Biochemistry ch.11-15

HIGH-ENERGY PHOSPHATES ACT AS THE

"ENERGY CURRENCY" OF THE CELL ATP is able to act as a donor of high-energy phosphate ADP can accept high-energy phosphate to form ATP from those compounds above ATP in the table.

After deamination, amino nitrogen is excreted as urea. and the carbon skeletons that remain after transamination may: go through what three stages?

(1) be oxidized to CO2 via the citric acid cycle, •(2) be used to synthesize glucose (gluconeogenesis), or •(3) form ketone bodies or acetyl CoA, (oxidized or used for synthesis of fatty acids) •Several amino acids are also the precursors of other compounds, (purines, pyrimidines, hormones such as epinephrine and thyroxine, and neurotransmitters).

monocarboxylic acids

(3-hydroxybutyric, acetoacetic, and acetic), in their undissociated, form. Long-chain fatty acids are transported into mitochondria via the carnitine system.

Newly synthesized (liver) triacylglycerol and dietary triacylglycerol are secreted as _____________

(VLDL).

Glycosides are widely distributed in nature; the aglycone may be methanol, glycerol, a sterol, a phenol, or a base such as adenine. The glycosides that are important in medicine because of their action on the heart___________ all contain steroids as the aglycone. These include derivatives of digitalis and strophanthus such as ________, an inhibitor of the Na+-K+-ATPase of cell membranes. Other glycosides include antibiotics such as ___________.

(cardiac glycosides) ouabain streptomycin

A number of drugs ___________ and ____________ inhibit oxidative phosphorylation, usually with fatal consequences.

(eg, amobarbital) , poisons (eg, cyanide, carbon monoxide)

Liver and kidney converts non-carbohydrate metabolites to glucose

(gluconeogenesis).

Excess Glucose is used to synthesize glycogen ________________ or fatty acids _________________.

(glycogenesis), (lipogenesis)

It is achieved by control of one or more key reactions in the pathway____________

(regulatory enzymes).

Or impaired sensitivity of tissues to insulin action ___________-leading to__________ derangement.

(type II diabetes) , metabolic

nucleoside diphosphate (NDP) kinases

, UTP, GTP, and CTP can be synthesized from their diphosphates, for example, UDP reacts with ATP to form UTP.

what are the Responses in adipose tissue to fasting: 3 answers. •This leads to release of ___________ (which is a substrate for gluconeogenesis in the liver) and _______________, which are used by _________,__________,__________- as their preferred metabolic fuel, sparing glucose.

1. A decrease in insulin and increase in glucagon results in inhibition of lipogenesis. 2. inactivation and internalization of lipoprotein lipase. 3. activation of intracellular hormone-sensitive lipase. glycerol, non-esterified fatty acids. liver, heart, and skeletal muscle

The more important types of isomerism found with glucose are as follows. 5 types

1. D and L isomerism: 2. Optical activity 3. Pyranose and furanose ring structures: 3. Alpha and beta anomers: 4. Epimers: 5. Aldose-ketose isomerism:

The cytosol is the location of: 1. 2. 3. 4.

1. Glycolysis 2•the pentose phosphate pathway 3•fatty acid synthesis all occur in the cytosol. 4•In gluconeogenesis, substrates such as lactate and pyruvate, which are formed in the cytosol, enter the mitochondrion, yield oxaloacetate as a precursor for gluconeogenisis in the cytosol.

Extracellular lipoprotein lipase: 1. The resultant non-esterified fatty acids are largely taken up by the __________ 2•used for synthesis of _____________ 3•glycerol is taken up in liver and used for either____________, ________ synthesis or -__________-. 4•Remaining FAs in bloodstream are taken up by the liver and re-esterified into___________.

1. tissue. 2. triacylglycerol. 3. gluconeogenesis, glycogen, lipogenesis 4. VLDLs

Acetyl-CoA formed by β-oxidation of fatty acids may undergo three fates (Figure 14-3):

1.As with acetyl-CoA arising from glycolysis, it is oxidized to CO2 + H2O via the citric acid cycle. 2.It is the precursor for synthesis of cholesterol and other steroids. 3.In the liver, it is used to form the ketone bodies, acetoacetate and 3-hydroxybutyrate which are important fuels in prolonged fasting and starvation.

Complex I

1.NADH-Q oxidoreductase (Complex I), where electrons are transferred from NADH to coenzyme Q (Q) (also called ubiquinone)

How many H's in George's name?

2

In oxidation reactions, the flavin (eg, FAD) accepts _________and _____ in ______steps, forming the ____________ followed by __________and the substrate is _______

2 electrons, 2 H+ in 2, semiquinone intermediate, the reduced flavin (eg, FADH2), oxidized.

In the reverse (reduction) reaction, the reduced flavin gives up ______and________ so that it becomes _________and the substrate is__________.

2 electrons, 2 H+, oxidized (eg, to FAD) ,reduced

the uncoupler that has been used most frequently is

2,4-dinitrophenol, but other compounds act in a similar manner.

Complex III

2.Q-cytochrome coxidoreductase (Complex III), which passes the electrons on to cytochrome c

Complex IV

3.cytochrome c oxidase (Complex IV), which completes the chain, passing the electrons to O2 and causing it to be reduced to H2O

Complex II

4.Some substrates with more positive redox potentials than NAD+/NADH (eg, succinate) pass electrons to Q via a fourth complex, succinate-Q reductase (Complex II), rather than Complex I.

A 70-kg adult human being requires 8 to 12 MJ (1920-2900 kcal) from metabolic fuels each day. Average physical activity increases metabolic rate only by about ____________

40% to 50% over BMR.

for biologic systems, the redox potential (E′0) is normally expressed at pH of what?

7.0, at which pH the electrode potential of the hydrogen electrode is −0.42 V.

Glycolysis.

A net formation of two ~Ⓟ results from the formation of lactate Located in the ctyosol

SUPEROXIDE DISMUTASE PROTECTS

AEROBIC ORGANISMS AGAINST OXYGEN TOXICITY

CARBOHYDRATES ARE __________DERIVATIVES OF POLYHYDRIC ALCOHOLS

ALDEHYDE OR KETONE

The importance of phosphates in intermediary metabolism became evident with the discovery of the role of

ATP, adenosine diphosphate (ADP), and inorganic phosphate (Pi) in glycolysis.

It is the precursor for synthesis of cholesterol and other steroids.

Acetyl-CoA

Much of Amino Acid Metabolism Involves Transamination: ______________are required for protein synthesis

Amino acids

________________and __________ resulting from the digestion are absorbed via the hepatic portal vein

Amino acids ,glucose

Coupling of dehydrogenation and hydrogenation reactions by an intermediate carrier. (graph,pg9)

An alternative method of coupling an exergonic to an endergonic process is to synthesize a compound of high-energy potential in the exergonic reaction and to incorporate this new compound into the endergonic reaction, thus effecting a transference of free energy from the exergonic to the endergonic pathway. The biologic advantage of this mechanism is that the compound of high potential energy, ~Ⓔ, unlike I in the previous system, need not be structurally related to A, B, C, or D, allowing Ⓔ to serve as a transducer of energy from a wide range of exergonic reactions to an equally wide range of endergonic reactions or processes, such as biosyntheses, muscular contraction, nervous excitation, and active transport. In the living cell, the principal high-energy intermediate or carrier compound (designated ~Ⓔ in Figure 11-3) is adenosine triphosphate (ATP)

inhibit the respiratory chain at Complex III.

Antimycin A and dimercaprol

Dioxygenases Incorporate Both

Atoms of Molecular Oxygen into the Substrate

ENDERGONIC PROCESSES PROCEED BY?

BY COUPLING TO EXERGONIC PROCESSES

__________,____________,_____________,-___________,___________are hydroxylated, increasing their solubility and excretion.

Benzpyrene, aminopyrine, aniline, morphine, and benzphetamine

isothermic

Biologic systems are essentially ____________ and use chemical energy to power living processes.

At the Tissue & Organ Level, the ____________Integrates Metabolism

Blood Circulation

Most human FAs are even numbered

C16, C18, C20

CARBOHYDRATES OCCUR IN _______,_______ Approximately 5% of the weight of cell membranes is the carbohydrate part of glycoproteins (see Chapter 46) and glycolipids. Their presence on the outer surface of the plasma membrane (the __________) has been shown with the use of plant lectins, proteins that bind specific glycosyl residues. For example, concanavalin A binds α-glucosyl and α-mannosyl residues. Glycophorin is a major integral membrane glycoprotein of human erythrocytes. It has 130 amino acid residues and spans the lipid membrane, with polypeptide regions outside both the external and internal (cytoplasmic) surfaces. Carbohydrate chains are attached to the amino terminal portion outside the external surface. Carbohydrates are also present in apo-protein B of plasma lipoproteins.

CELL MEMBRANES & IN LIPOPROTEINS. glycocalyx.

: an increased rate of protein catabolism, associated with advanced cancer, COPD and TB.

Cachexia

________ are widely distributed and have important structural and metabolic roles.

Carbohydrates

Ionophores Permit Specific_________ to Penetrate Membranes

Cations

is the chief constituent of plant cell walls. It is insoluble and consists of β-D-glucopyranose units linked by β1 → 4 bonds to form long, straight chains strengthened by cross-linking hydrogen bonds. Mammals lack any enzyme that hydrolyzes the β1 → 4 bonds, and so cannot digest cellulose. It is an important source of "bulk" in the diet, and the major component of dietary fiber. Microorganisms in the gut of ruminants and other herbivores can hydrolyze the linkage and ferment the products to short-chain fatty acids as a major energy source. There is some bacterial metabolism of cellulose in the human colon.

Cellulose

Glucose Is Required by the_________-,_________

Central Nervous System and Erythrocytes

is a structural polysaccharide in the exoskeleton of crustaceans and insects, and also in mushrooms. It consists of N-acetyl-D-glucosamine units joined by β1 → 4 glycosidic bonds.

Chitin

distribute dietary lipids and, the largest of the plasma lipoproteins, are especially rich in triacylglycerol.

Chylomicrons

The Q Cycle Couples Electron Transfer to Proton Transport in ________ Electrons are passed from _______________

Complex III, QH2 to cytochrome c via Complex III (Q-cytochrome coxidoreductase):

Glycolysis Occurs in the ___________ & the _______________in the Mitochondria: •Compartmentation permits integration and regulation of ________________.

Cytosol, Citric Acid Cycle. metabolism. •Not all pathways are of equal importance in all cells.

marasmus

Death from starvation occurs when available energy reserves are depleted, and certain forms of malnutrition are associated with energy imbalance.

are intermediates in the hydrolysis of starch

Dextrins

are condensation products of two monosaccharide units, for example, lactose, maltose, isomaltose, sucrose, and trehalose.

Disaccharides

The Q cycle:

During the oxidation of QH2 to Q, one electron is donated to cyt c via a Rieske Fe-S and cyt c1 and the second to a Q to form the semiquinone via cyt βL and cyt βH, with 2H+ being released into the intermembrane space. A similar process then occurs with a second QH2, but in this case the second electron is donated to the semiquinone, reducing it to QH2, and 2H+ are taken up from the matrix. (cyt, cytochrome; Fe-S, iron-sulfur protein; Q, coenzyme Q or ubiquinone.)

Catalase Uses Hydrogen Peroxide as

Electron Donor & Electron Acceptor

Ion Transport in Mitochondria Is

Energy Linked Mitochondria maintain or accumulate cations such as K+, Na+, Ca2+, and Mg2+, and Pi. It is assumed that a primary proton pump drives cation exchange.

oxidoreductases and are classified into four groups:

Enzymes involved in oxidation and reduction are. oxidases, dehydrogenases, hydroperoxidases, and oxygenases

obesity

Excess storage of surplus energy causes

is synthesized and activated in response to insulin: (adipose and skeletal muscle)

Extracellular lipoprotein lipase

cytochromes Class I systems:

FAD-containing reductase enzyme, iron sulfur (Fe2S2) protein and P450 heme protein

FAD accepts 2 electrons and 2 H+ in the reaction forming

FADH2

Metabolic Fuel Reserves Are Mobilized in the __________ State

Fasting. There is a small fall in plasma glucose in the fasting state, and then little change as fasting is prolonged into starvation. Plasma nonesterified fatty acids increase in fasting, but then rise little more in starvation; as fasting is prolonged, the plasma concentration of ketone bodies (acetoacetate and 3-hydroxybutyrate) increases markedly

Lipid Metabolism Is Concerned Mainly With

Fatty Acids & Cholesterol

The end product of a pathway inhibits the enzyme catalyzing an early reaction.

Feed back:

A precursor well before the step acts as an activator.

Feed forward:

The Flux-Generating Reaction Is the ___________ in a Pathway That Is Saturated With the ___________

First Reaction, Substrate

_________are important components of Complexes I and II.

Flavoproteins

Components of the Respiratory Chain Are Contained in _____________

Four Large Protein Complexes Embedded in the Inner Mitochondrial Membrane

6.Aldose-ketose isomerism:

Fructose has a keto group in position 2, the anomeric carbon of fructose. Glucose has a potential aldehyde group in position 1 the anomeric carbon. Chemically, aldoses are reducing sugars. Benedicts Reagent: a simple chemical test for glucose in urine in poorly controlled diabetes mellitus, by reduction of an alkaline copper solution.

In the fasting state, __________________ is in intracellular vesicles.

GLUT-4 (glucose transporter of muscle and adipose tissue)

Nonequilibrium Reactions Are Potential Control Points to ___________

Generate Flux

________: Secreted by α cells of the pancreas: •inhibits ___________ synthetase •activates ______________in the liver. •Glucose-6-phosphate is hydrolyzed by _______and_______ is released (from liver

Glucagon. glycogen. glycogen phosphorylase. glucose 6-phosphatase, and glucose

_________ is 2-amino-D-galactopyranose. Both _______,_________ occur as N-acetyl derivatives in complex carbohydrates, for example, glycoproteins.

Glucosamine (2-amino-D-glucopyranose) (α form). Galactosamine, glucosamine and galactosamine .

is the major metabolic fuel of mammals (except ruminants) and a universal fuel of the fetus.

Glucose

is the most important carbohydrate; most dietary carbohydrate is formed by hydrolysis of dietary starch and disaccharides, or other sugars converted to glucose.

Glucose

___________, the major fuel of most tissues is metabolized to pyruvate by the pathway of___________.

Glucose, glycolysis

is the study of the roles of sugars in health and disease.

Glycobiology

_________ is the storage polysaccharide in animals and is sometimes called animal starch. It is a more highly branched structure than amylopectin, with chains of 12 to 15 α-D-glucopyranose residues (in α1 → 4 glucosidic linkage) with branching by means of α1 → 6 glucosidic bonds. Muscle glycogen granules (β-particles) are spherical and contain up to 60,000 glucose residues; in liver there are similar granules and also rosettes of glycogen granules that appear to be aggregated β-particles.

Glycogen

what are the three major sources of ~Ⓟ "energy capture":

Glycolysis. Oxidative phosphorylation: The citric acid cycle Phosphagens:

is the comprehensive study of glycomes, including genetic, physiological, pathological.

Glycomics

________ are proteins containing branched or unbranched oligosaccharide chains (Table 15-5),__________(Figure 15-15). They occur in cell membranes (see Chapters 40 and 46) and many proteins are glycosylated. The _________are N- or O-acyl derivatives of neuraminic acid (Figure 15-15). ___________ is a nine-carbon sugar derived from mannosamine (an epimer of glucosamine) and pyruvate. Sialic acids are constituents of both ________ and ___________.

Glycoproteins (also known as mucoproteins), including fucose, sialic acids. Neuraminic acid. glycoproteins, gangliosides

are complex carbohydrates containing amino sugars and uronic acids.

Glycosaminoglycans (mucopolysaccharides). They may be attached to a protein molecule to form a proteoglycan. Proteoglycans provide the ground or packing substance of connective tissue (see Chapter 50). They hold large quantities of water and occupy space, thus cushioning or lubricating other structures, because of the large number of —OH groups and negative charges on the molecule, which, by repulsion, keep the carbohydrate chains apart. Examples are hyaluronic acid, chondroitin sulfate, and heparin

are formed by condensation between the hydroxyl group of the anomeric carbon of a monosaccharide, and a second compound that may be another monosaccharide or, in the case of an ________, not a sugar

Glycosides, aglycone

Na+ can be exchanged for__________, driven by _____________ It is believed that active uptake of ________by __________occurs with a_______________, possibly through a ______________. Calcium release from______________ is facilitated by exchange with ____________.

H+, the proton gradient, Ca2+, mitochondria, net charge transfer of 1 (Ca+ uniport), Ca2+/H+ antiport. mitochondria, Na+

OXIDASES USE OXYGEN AS A

HYDROGEN ACCEPTOR

Cytochrome Oxidase Is a

Hemoprotein

• is such a flux-generating step .

Hexokinase. •Later reactions then control the rate of flux through the pathway

Amino Sugars (___________) Are Components of Glycoproteins, Gangliosides, & Glycosaminoglycans The amino sugars include_________ a constituent of hyaluronic acid, D-galactosamine (also known as chondrosamine), a constituent of chondroitin, and D-mannosamine.

Hexosamines, D-glucosamine,

Adenylate kinase is important for the maintenance of energy homeostasis in cells because it allows:

High-energy phosphate in ADP to be used in the synthesis of ATP. The AMP formed as a consequence of activating reactions involving ATP to rephosphorylated to ADP. AMP to increase in concentration when ATP becomes depleted so that it is able to act as a metabolic (allosteric) signal to increase the rate of catabolic reactions, which in turn lead to the generation of more ATP

act rapidly by altering the activity of existing enzymes, or altering enzyme synthesis

Hormones

Q Accepts Electrons via Complexes

I & II

Iron-sulfur proteins (non-heme iron proteins, Fe-S)are found in Complexes

I, II, and III.

Molecular Oxygen Is Reduced to Water via Complex ________

IV Reduced cytochrome c is oxidized by Complex IV (cytochrome c oxidase), with the concomitant reduction of O2 to two molecules of water. Electrons are passed initially to a Cu center (CuA), which contains 2Cu atoms linked to two protein cysteine-SH groups (resembling an Fe-S), then in sequence to heme a, heme a3, a second Cu center, CuB, which is linked to heme a3, and finally to O2. Of the eight H+ removed from the matrix, four are used to form two water molecules and four are pumped into the intermembrane space. Thus, for every pair of electrons passing down the chain from NADH or FADH2, 2H+ are pumped across the membrane by Complex IV. The O2 remains tightly bound to Complex IV until it is fully reduced, and this minimizes the release of potentially damaging intermediates such as superoxide anions or peroxide which are formed when O2 accepts one or two electrons,

When ATP Forms AMP,

Inorganic Pyrophosphate (PPi) Is Produced ATP can also be hydrolyzed directly to AMP, with the release of PPi . This occurs, for example, in the activation of long-chain fatty acids

: Secreted by the pancreatic β-islet cells in response to increased glucose in the portal blood.

Insulin

Fed State; __________ regulates blood glucose and tissue uptake:

Insulin

________ take up glucose from the bloodstream in the presence of the hormone.

Insulin-sensitive tissues

________ is a polysaccharide of fructose (a fructosan) found in tubers and roots of dahlias, artichokes, and dandelions. I t is readily soluble in water and is used to determine the glomerular filtration rate (see Chapter 48), but it is not hydrolyzed by intestinal enzymes, so has no nutritional value.

Inulin

Sugars Exhibit Various Forms of ________: Glucose, with four asymmetric carbon atoms, can form ________

Isomerism. 16 isomers.

5.Epimers:

Isomers differing as a result of variations in configuration of the —OH and —H on carbon atoms 2, 3, and 4 of glucose are known as epimers. Biologically, the most important epimers of glucose are mannose (epimerized at carbon 2) and galactose (epimerized at carbon 4) (Figure 15-5).

_____________are exported to extrahepatic tissues, as fuel in prolonged fasting and starvation.

Ketone bodies

______________ are major metabolic fuel for skeletal and heart muscle and can meet up to 20% of the brain's energy needs.

Ketones

Examples of flavoprotein oxidases include

L-amino acid oxidase.

NADH-Q oxidoreductase or Complex I is a large

L-shaped multisubunit protein that catalyzes electron transfer from NADH to Q, coupled with the transfer of four H+ across the membrane. Electrons are transferred from NADH to FMN initially, then to a series of Fe-S centers, and finally to Q

____________________: Fatty acids cannot be used for the synthesis of glucose. •acetyl-CoA can never be used for gluconeogenesis. •Instead acetyl-CoA is condensed into Ketones for export to most tissues •propionyl CoA and glycerol released by lipolysis can be used for gluconeogenisis.

Liopolysis

_______________: Carbohydrate can be used for synthesis of fatty acids, (triacylglycerides) in adipose tissue and liver (exported via VLDLs) A high intake of fat inhibits lipogenesis in the adipose tissue and liver

Lipogenesis:

Ionophores: and examples

Lipophilic molecules that complex cations and facilitate transport through membranes, (valinomycin (K+), dinitrophenol is a proton ionophores.

____________,___________ yield acetyl-CoA on oxidation, and hence cannot be used for gluconeogenesis,

Llysine and leucine

METABOLIC PATHWAYS MAY BE STUDIED AT DIFFERENT LEVELS OF ORGANIZATION: ____________of metabolic pathways is revealed by studies at two levels of organization.

Location and integration

The value for the hydrolysis of the terminal phosphate of ATP divides the list into two groups: what are these group?

Low-energy phosphates High-energy phosphates

_____,______,______Are Important Disaccharides The disaccharides are sugars composed of two monosaccharide residues linked by a glycoside bond (Figure 15-11). The physiologically important disaccharides are maltose, sucrose, and lactose (Table 15-4). Hydrolysis of sucrose yields a mixture of glucose and fructose called "invert sugar" because fructose is strongly levorotatory and changes (inverts) the weaker

Maltose, Sucrose, & Lactose

dehydrogenations.

Many biologic oxidations can take place without the participation of molecular oxygen

Cytochromes

May Also Be Regarded as Dehydrogenases. are iron-containing hemoproteins: •the iron atom oscillates between Fe3+ and Fe2+ during oxidation and reduction. •they are classified as dehydrogenases (except for cytochrome oxidase (previously described), . •they are involved as carriers of electrons from flavoproteins to cytochrome oxidase. •Several identifiable cytochromes occur in the respiratory chain, ie, cytochromes b, c1, c, and cytochrome oxidase. •Cytochromes are also found in other locations, for example, the endoplasmic reticulum (cytochromes P450 and b5), and in plant cells, bacteria, and yeasts.

Cytochromes P450 Are

Monooxygenases Important in Steroid Metabolism & for the Detoxification of Many Drugs

Carbohydrates are classified as follows:

Monosaccharides, Disaccharides, Oligosaccharides, Polysaccharides, Nonstarch polysaccharides

____________are simple sugars. They may be classified as ___,___,____,__,___ depending upon the number of carbon atoms (3-7), and as _______,______- depending on whether they have an aldehyde or ketone group.

Monosaccharides, trioses, tetroses, pentoses, hexoses, or heptoses. aldoses or ketoses,

MANY POISONS INHIBIT THE RESPIRATORY CHAIN

Much information about the respiratory chain has been obtained by the use of inhibitors, and, conversely, this has provided knowledge about the mechanism of action of several poisons (Figure 13-9). They may be classified as inhibitors of the respiratory chain, inhibitors of oxidative phosphorylation, or uncouplers of oxidative phosphorylation.

Electrons flow through the respiratory chain through a redox span of 1.1 V from

NAD+/NADH to O2/2H2O passing through three large protein complexes

Many Dehydrogenases Depend on

Nicotinamide Coenzymes: Nicotinamide Adenine Dinucleotide (NAD+) or Nicotinamide Adenine Dinucleotide Phosphate (NADP+)

Explain the Oxidation and reduction of nicotinamide coenzymes

Nicotinamide coenzymes consist of a nicotinamide ring linked to an adenosine via a ribose and a phosphate group, forming a dinucleotide. NAD+/NADH are shown, but NADP+/NADPH are identical except that they have a phosphate group esterified to the 2′OH of the adenosine. An oxidation reaction involves the transfer of two electrons and one H+ from the substrate to the nicotinamide ring of NAD+ forming NADH and the oxidized product. The remaining hydrogen of the hydrogen pair removed from the substrate remains free as a hydrogen ion.

are the major component of dietary fiber. (cellulose and inulin)

Nonstarch polysaccharides:

Special exchange transporters span the membrane to allow ions such as ____________ to pass through without ___________________across the membrane.

OH−, ATP4−, ADP3−, and metabolites. discharging the electrochemical gradient

DEHYDROGENASES CANNOT USE __________ AS A __________

OXYGEN, HYDROGEN ACCEPTOR

If the intake of metabolic fuels is greater than energy expenditure, the surplus is stored, largely as triacylglycerol in adipose tissue, leading to the development of

Obesity

encode biological information and that this depends upon their constituent sugars, their sequences, and their linkage

Oligosaccharide chains

are condensation products of three to ten monosaccharides. Most are not digested by human enzymes.

Oligosaccharides

Monooxygenases (Mixed-Function Oxidases, Hydroxylases) Incorporate Only

One Atom of Molecular Oxygen Into the Substrate. The other oxygen atom is reduced to water, an additional electron donor or cosubstrate (Z)

The citric acid cycle

One ~Ⓟ is generated directly in the cycle at the succinate thiokinase

Deoxy Sugars Lack an _________ Atom Deoxy sugars are those in which one hydroxyl group has been replaced by __________. An example is deoxyribose (Figure 15-9) in DNA. The deoxy sugar L-fucose (Figure 15-15) occurs in glycoproteins; 2-deoxyglucose is used experimentally as an inhibitor of glucose metabolism.

Oxygen, hydrogen,

cytochrome P450 system.

Oxygenases incorporate oxygen; many drugs, pollutants, and chemical carcinogens (xenobiotics) are metabolized by enzymes of this class, known as the

occurs in fruits; it is a polymer of galacturonic acid linked α-1→ 4, with some galactose an/or arabinose branches, and is partially methylated

Pectin

________,_______,_______-,_________ give rise to both acetyl-CoA and intermediates that can be used for gluconeogenesis.

Phenylalanine, tyrosine, tryptophan, and isoleucine

The H+/Pi symport is equivalent to the

Pi/OH− antiport

are condensation products of more than ten monosaccharide units (starches and dextrins) which may be linear or branched polymers. (hexosans or pentosans).

Polysaccharides

Insulin stimulates __________ synthesis. (up to 20% of resting energy expenditure after a meal, but only 9% in the fasting state.)

Protein

Carbohydrate Metabolism Is Centered on the __________-,_________:

Provision & Fate of Glucose

FREE ENERGY CHANGES CAN BE EXPRESSED IN TERMS OF

REDOX POTENTIAL

THE RESPIRATORY CHAIN OXIDIZES

REDUCING EQUIVALENTS & ACTS AS A PROTON PUMP

THE FLUX OF METABOLITES THROUGH METABOLIC PATHWAYS MUST BE ____________:

REGULATED. Regulation of the overall flux is important to ensure an appropriate supply of the products

THE CHEMIOSMOTIC THEORY CAN ACCOUNT FOR

RESPIRATORY CONTROL AND THE ACTION OF UNCOUPLERS

The flux through this pathway can be regulated by the availability of substrate A. Flux is also determined by removal of the end product D the availability of co-substrates or cofactors represented by X and Y also play a role.

Reactions A ↔ B and C ↔ D are equilibrium reactions and B → C is a non-equilibrium reaction.

oxidative phosphorylation.

Respiration is coupled to the generation of the high-energy intermediate, ATP

POLYSACCHARIDES SERVE _______,_______ Polysaccharides include a number of physiologically important __________. ________ is a homopolymer of glucose forming an α-glucosidic chain, called a _______. It is the most important dietary carbohydrate in cereals, potatoes, legumes, and other vegetables. The two main constituents are ________ (13%-20%), which has a nonbranching helical structure, and ________ (80%-87%), which consists of branched chains consists of 24 to 30 glucose residues with α1 → 4 linkages in the chains and by α1 → 6 linkages at the branch points

STORAGE & STRUCTURAL FUNCTIONS carbohydrates. Starch. glucosan or glucan. amylose., amylopectin

A Proton-Translocating Transhydrogenase Is a

Source of Intra-mitochondrial NADPH

each cell organelle (eg, the mitochondrion) or compartment (eg, the cytosol) has specific roles that form part of a subcellular pattern of metabolic pathways.

Subcellular level:

Oxidation of Extra-mitochondrial NADH Is Mediated by

Substrate Shuttles

Cytochrome P450:

Superfamily of heme-containing monooxygenases >50 such enzymes have been found in the human genome. In the endoplasmic reticulum in the liver and intestine, also found in the mitochondria in some tissues.

OXYGENASES CATALYZE

THE DIRECT TRANSFER & INCORPORATION OF OXYGEN INTO A SUBSTRATE MOLECULE

SPECIFIC ENZYMES ARE ASSOCIATED WITH COMPARTMENTS SEPARATED BY

THE MITOCHONDRIAL MEMBRANES

1.D and L isomerism:

The D form or its mirror image as the L form and determined by its spatial relationship to the parent compound glycerose (glyceraldehyde). The L and D forms of this sugar, and of glucose, are shown below. The orientation of the H and OH groups at carbon 5 in glucose determines D or L. When the —OH group is on the right it is the D isomer; when on the left, it is L. Most of the naturally occurring monosaccharides are D sugars, and the enzymes responsible for their metabolism are specific for this configuration.

metabolism

The combined catabolic and anabolic processes constitute

Coupling of an exergonic to an endergonic reaction (graph,pg8)

The conversion of metabolite A to metabolite B occurs with release of free energy and is coupled to another reaction in which free energy is required to convert metabolite C to metabolite D. The basis for the concept of respiratory control. (prevents spontaneous combustion!)

Mechanism of ATP production by ATP synthase.

The enzyme complex consists of an F0subcomplex which is a disk of "C" protein subunits. Attached is a γ subunit in the form of a "bent axle." Protons passing through the disk of "C" units cause it and the attached γ subunit to rotate. The γ subunit fits inside the F1 subcomplex of three α and three β subunits, which are fixed to the membrane and do not rotate. ADP and Pi are taken up sequentially by the β subunits to form ATP, which is expelled as the rotating γ subunit squeezes each β subunit in turn and changes its conformation. Thus, three ATP molecules are generated per revolution. For clarity, not all the subunits that have been identified are shown—eg, the "axle" also contains an ε subunit.

The Mitochondria contains:

The enzymes of the citric acid cycle and β-oxidation, the respiratory chain complexes, and for oxidative phosphorylation.

catabolism

The exergonic reactions, the breakdown or oxidation of fuel molecules

Respiratory Control Ensures a Constant Supply of ATP

The rate of respiration of mitochondria can be controlled by the availability of ADP. This is because oxidation and phosphorylation are tightly coupled; that is, oxidation cannot proceed via the respiratory chain without concomitant phosphorylation of ADP. Table 13-1shows the five conditions controlling the rate of respiration in mitochondria. Most cells in the resting state are in state 4, and respiration is controlled by the availability of ADP. When work is performed, ATP is converted to ADP, allowing more respiration to occur, which in turn replenishes the store of ATP. Under certain conditions, the concentration of inorganic phosphate can also affect the rate of functioning of the respiratory chain. As respiration increases (as in exercise), the cell approaches state 3 or 5 when either the capacity of the respiratory chain becomes saturated or the PO2 decreases below the Km for heme a3. There is also the possibility that the ADP/ATP transporter, which facilitates entry of cytosolic ADP into and ATP out of the mitochondrion, becomes rate limiting.

4.Alpha and beta anomers: •

The ring structure of an aldose is a •the ring structure of a ketose is a hemiketal. Crystalline glucose is α-D-glucopyranose. The cyclic structure is retained in the solution, but isomerism occurs about position 1, the carbonyl or anomeric carbon atom, to give a mixture of α-glucopyranose (38%) and β-glucopyranose (62%). •Less than 0.3% is represented by α and β anomers of glucofuranose.

creatine phosphate shuttle

The shuttle allows rapid transport of high-energy phosphate from the mitochondrial matrix into the cytosol. (CKa, creatine kinase concerned with large requirements for ATP, eg, muscular contraction; CKc, creatine kinase for maintaining equilibrium between creatine and creatine phosphate and ATP/ADP; CKg, creatine kinase coupling glycolysis to creatine phosphate synthesis; CKm, mitochondrial creatine kinase mediating creatine phosphate production from ATP formed in oxidative phosphorylation; P, pore protein in outer mitochondrial membrane.)

coupling

The vital processes obtain energy by chemical linkage,__________to oxidative reactions. The terms exergonic and endergonic, rather than the normal chemical terms "exothermic" and "endothermic."

ATP Allows the Coupling of

Thermodynamically Unfavorable Reactions to Favorable Ones

the glycerophosphate shuttle is shown in Figure 13-12.

This shuttle is present in some tissues (eg, brain, white muscle), looses 1 ATP (3:2 yield).

metabolic rate

Thyroid hormones control it, and its the rate of energy release).

The Creatine Phosphate Shuttle Facilitates

Transport of High-Energy Phosphate from Mitochondria

is the main fuel reserve of the body.

Triacylglycerol (adipose)

HYDROPEROXIDASES

USE HYDROGEN PEROXIDE OR AN ORGANIC PEROXIDE AS SUBSTRATE. contribute to the causation of diseases such as cancer and atherosclerosis. •contribute to the aging process in general.

Peroxidases Reduce Peroxides Using

Various Electron Acceptors. found in milk and in leukocytes, platelets, and other tissues •Their prosthetic group is protoheme. •hydrogen peroxide is reduced at the expense of several electron acceptors, •such as ascorbate (vitamin C), quinones, and cytochrome c.

2.The presence of asymmetric carbon atoms confers optical activity on compounds.

When a beam of plane-polarized light is passed through an optical isomer, it rotates either •to the right, dextrorotatory (+), •or to the left, levorotatory (−). The direction of rotation of polarized light is independent of the stereochemistryso it may be designated D(−), D(+), L(−), or L(+). For example, the naturally occurring form of fructose is the D(−) isomer. Confusingly, dextrorotatory (+) was at one time called D-, and levorotatory (−) L-. It is unrelated to D- and L-isomerism. In solution, glucose is dextrorotatory, and glucose is known as dextrose.

Energy-linked transhydrogenase:

a protein in the inner mitochondrial membrane, couples the passage of protons down the electrochemical gradient from outside to inside the mitochondrion with the transfer of H from intra-mitochondrial NADH to NADPH for intra-mitochondrial enzymes.

If the second group is also a hydroxyl, the O-glycosidic bond is an ________ link because it results from a reaction between a hemiacetal group (formed from an aldehyde and an —OH group) and another —OH group.

acetal

The ketone bodies are _________,_______,_________-

acetoacetate, 3-hydroxybutyrate, and acetone (which is formed nonenzymically by decarboxylation of acetoacetate).

As fasting becomes more prolonged, Liver forms more ___________ than can be oxidized

acetyl-CoA

Fatty acids are oxidized to _______________, or esterified with____________, forming triacylglycerol.

acetyl-CoA (β-oxidation), glycerol

Aerobic tissues metabolize pyruvate to ___________, which enters the citric acid cycle for oxidation to CO2 and H2O, linked to the formation of ATP in ____________

acetyl-CoA, oxidative phosphorylation.

Coma results from both the

acidosis and also the considerably increased osmolality.

Combination of phosphate transporter with the ____________________in ATP synthesis.

adenine nucleotide transporter

In starvation, as _________ is depleted, there is an increase in the rate of _____________.

adipose, protein catabolism

(SOD) superoxide dismutase protects

aerobic organisms against the effects of superoxide. The enzyme occurs in all major aerobic tissues in the mitochondria and the cytosol.

Enzymes catalyzing non-equilibrium reactions are often regulated ______________

allosteric modifiers:

Pyruvate and intermediates of the citric acid cycle for the synthesis of nonessential or dispensable __________. and _____________ is the precursor of_________-,__________-

amino acids, acetyl-CoA, fatty acids and cholesterol.

The resultant amino acids are largely exported back to muscle, to provide ______________ for formation of more __________, while the ________ provides a substrate for gluconeogenesis in the ____________

amino groups, alanine, pyruvate, liver

Uncouplers (eg, dinitrophenol) are

amphipathic (see Chapter 21) and increase the permeability of the lipoid inner mitochondrial membrane to protons, thus reducing the electrochemical potential and short-circuiting the ATP synthase (Figure 13-7). In this way, oxidation can proceed without phosphorylation

aldehyde dehydrogenase, and contains_________

an FAD-linked enzyme which contains molybdenum and nonheme iron

Although exposure of animals to an atmosphere of 100% oxygen causes

an adaptive increase in SOD, particularly in the lungs, prolonged exposure leads to lung damage and death.

Glycolysis can also occur__________ when the end product is lactate and fewer ATP.

anaerobically (in the absence of oxygen)

NADP-linked dehydrogenases

are found characteristically biosynthetic pathways where reductive reactions are required, as in the extramitochondrial pathway of fatty acid synthesis and steroid synthesis —and also in the pentose phosphate pathway

Antioxidants, eg, α-tocopherol (vitamin E), act

as scavengers of free radicals and reduce the toxicity of oxygen

reduction

as the gain of electrons.

The liver regulates the

blood concentration of these water-soluble metabolites

In fasting and starvation glucose and glycogen reserves are used by the______________

brain and red blood cells.

The coenzymes (NAD+ and NADP+) are reduced by________________and reoxidized by _______________

by the specific substrate of the dehydrogenase , a suitable electron acceptor.

In ____________ as a result of the release of _________ (in response to tumors and disease), there is an increase in tissue protein ___________, and ____________- becoming a state of advanced starvation.

cachexia, cytokines, catabolism, increased metabolic rate,

In skeletal muscle, cytoplasmic _______ ion increases (response to nerve stimulation) stimulates _______the migration and activation without insulin.

calcium, GLUT 4

Between meals, reserves of _________________), )_______________-), and ___________ stores release energy molecules.

carbohydrate (glycogen in liver and muscle), lipid (triacylglycerol in adipose tissue, labile protein

The mitochondrion is the focus of _________,____________,and________-. •contains the enzymes of the 1._________ 2:_________ 3:________ 4:________ 5:___________

carbohydrate, lipid, and amino acid metabolism. 1. citric acid cycle 2•β-oxidation of fatty acids 3•ketogenesis 4•the respiratory chain and 5•ATP synthase

Animals can synthesize __________ from amino acids, but most are derived ultimately from plants. It is the precursor for synthesis of all the other carbohydrates in the body.

carbohydrates

Plants synthesize glucose from ______ and ______by photosynthesis and store it as ________and _______ of the plant cell walls.

carbon dioxide and water. starch and cellulose

The phospholipid___________ is concentrated in the inner membrane together with the __________,____________,____________

cardiolipin, enzymes of the respiratory chain, ATP synthase, and various membrane transporters.

NADH dehydrogenase acts as a

carrier of electrons between NADH and the components of higher redox potential

In the fasting state, glucose must be spared for use by the ____________and____________. -_____________- oxidize fatty acids and -the liver synthesizes ___________- from fatty acids to export to other tissues.

central nervous system and red blood cells. muscle and liver. ketone bodies

All the products of digestion are metabolized to a __________,___________ which is then oxidized by the ____________

common product, acetyl-CoA. citric acid cycle.

The antibiotic oligomycin

completely blocks oxidation and phosphorylation by blocking the flow of protons through ATP synthase

Fasting state;what happens to the glucose, insulin?

concentration of glucose in the portal blood falls, Glucagon is released: •insulin secretion decreases •skeletal muscle and adipose tissue take up less glucose.

Normally, the rate of tissue protein catabolism is __________ throughout the day:

constant

cytochromes Class II systems

contain cytochrome P450 reductase which passes electrons from FADH2 to FMN.

In vivo, ("steady-state") there is a net flux from left to right due to: 1. 2.

continuous supply of substrate A •continuous removal of product D.

Many well-known poisons such as __________ by inhibition of the ________

cyanide arrest respiration, respiratory chain.

In turn, the creatine phosphate is transported into the

cytosol via protein pores in the outer mitochondrial membrane, becoming available for generation of extramitochondrial ATP.

NADH is produced continuously in the_____________ by ______________, in___________.

cytosol, 3-phosphoglyceraldehyde dehydrogenase, glycolysis

Glycerophosphate shuttle for transfer of reducing equivalents from the__________ into the_____________.

cytosol, mitochondrion. This exchange of 1 NADH for 1 FADH2 looses the equivalent energy of 1 ATP so is less efficient than the Malate shuttle (next). This is found in most somatic tissues (muscle, brain).

The flavin groups such as FMN and FAD are associated with

dehydrogenases and oxidases

In solution, glucose is dextrorotatory, and glucose is known as .

dextrose

In _____________, there is either impaired synthesis and secretion of insulin

diabetes mellitus, (type I diabetes).,

Diseases associated with carbohydrate metabolism include

diabetes mellitus, galactosemia, glycogen storage diseases, and lactose intolerance.

The diet sets the basic pattern of metabolism (_________,__________,___________).

dietary carbohydrate, lipid, and protein. •Mainly glucose, fatty acids and glycerol, and amino acids.

The source of long-chain fatty acids is either_________ and __________from acetyl-CoA.

dietary lipid or de novo synthesis

Fatal infantile mitochondrial myopathy and renal dysfunction caused by what

diminution or absence of most oxidoreductases of the respiratory chain.

Oxygenases may be divided into two subgroups,

dioxygenases and monooxygenases.

Uncouplers

dissociate oxidation in the respiratory chain from phosphorylation (Figure 13-7). These compounds are toxic in vivo, causing respiration to become uncontrolled, since the rate is no longer limited by the concentration of ADP or Pi.

Aerobic organisms respiration is more

effecient than anaerobic organisms.

The cytochromes participate in an

electron transport chain in which both NADH and NADPH may donate reducing equivalents involving FAD or FMN.

Most of the riboflavin-linked dehydrogenases are concerned with _______

electron transport in (or to) the respiratory chain.

If the intake of metabolic fuels is consistently lower than energy expenditure,________________, wasting, and eventually, death will occur.

emaciation

Oxidative phosphorylation converts and traps as

energy as NTP's (phosphate).

Growing children have a proportionally higher requirement to allow for the _________

energy cost of growth. This energy requirement is met from carbohydrates (40%-60%), lipids (mainly triacylglycerol, 30%-40%), and protein (10%-15%), as well as alcohol. The mix depends on whether the subject is in the fed or fasting state, and on the duration and intensity of physical work.

At equilibrium, the forward and reverse reactions occur at

equal rates, no net flux in either direction.

The standard free-energy change can be calculated from what?

equilibrium constant Keq

Reactions A ↔ B and C ↔ D are ___________ reactions and B → C is a ______________ reaction.

equilibrium, non-equilibrium

Several antibiotics (eg, _________) contain amino sugars, which are important for their antibiotic activity.

erythromycin

The _______________or _______________must be supplied in the diet , since they cannot be synthesized in the body.

essential , indispensable amino acids

Death can result if _________- are catabolized and not replaced

essential tissue proteins

The adenine nucleotide transporter allows the

exchange of ATP and ADP, but not AMP. Since in this translocation four negative charges are removed from the matrix for every three taken in, the electrochemical gradient across the membrane (the proton motive force) favors the export of ATP

Exchange diffusion systems

exchange of anions and cations and are necessary for uptake and output of ionized metabolites while preserving electrical and osmotic equilibrium

Under aerobic conditions,____________-does not accumulate and is____________ in________________-.

extra-mitochondrial NADH, oxidized, mitochondria

There is net protein catabolism in the ________ state. •

fasting

Net protein synthesis in the________ state, (increases by 20% to 25%).

fed

Flavoprotein enzymes contain as prosthetic groups.

flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD)

The relative positions of redox systems in the table allow prediction of the direction of

flow of electrons from one redox couple to another.

Role of the respiratory chain of mitochondria in the conversion of

food energy to ATP.

Cytochromes P450 and b5 are responsible

for 75% of the modification and degradation of drugs

redox potential (E′0).

free energy change in terms of ΔG0′ can be expressed as an oxidation-reduction

. Amino acids which yield TCA intermediates are classified as .

glucogenic

As glycogen reserves become depleted, amino acids arising are used for________________.

gluconeogenesis

Pyruvate can then be carboxylated to oxaloacetate, a substrate for _________.

gluconeogenesis

In the fed state, the metabolic fuel for most tissues is______-

glucose

For several hours after a meal, __________ is the major fuel for oxidation in most tissues; this is observed as an increase in the respiratory quotient (the ratio of carbon dioxide produced/oxygen consumed) from about 0.8 in the fasting state to near 1.

glucose,

•In starvation, ________ is less than 10% of whole body energy-yielding ___________-.

glucose, metabolism

Muscle cannot export _________- to ____________:

glucose, plasma

muscle lacks _____________-

glucose-6-phosphatase

If the hemiacetal portion is glucose, the resulting compound is a _________; if galactose, a _________; and so on.

glucoside, galactoside

The extent to which starch in foods is hydrolyzed by amylase is determined by its structure, the degree of crystallization or hydration (the result of cooking), and whether it is enclosed in intact (and indigestible) plant cells walls. The ________of a starchy food is a measure of its digestibility, based on the extent to which it raises the blood concentration of glucose compared with an equivalent amount of glucose or a reference food such as white bread or boiled rice. Glycemic index ranges from 1 (or 100%) for starches that are readily hydrolyzed in the small intestine to 0 for those that are not hydrolysed at all.

glycemic index

Triacylglycerol (adipose) hydrolyzed (lipolysis) to __________,_________:

glycerol and non-esterified (free) fatty acids

Triose phosphate intermediates in glycolysis give rise to the____________ of triacylglycerols.

glycerol moiety

the synthesis of ___________- in skeletal muscle and liver

glycogen

Ketogenesis in Fasting: Liver and muscle _________ are exhausted after about 18 hours. •Muscle cannot meet all of its energy requirements by__________. •Liver has __________- capacity for __________than for its own energy needs.

glycogen. β-oxidation greater, β-oxidation

Between meals, the liver breaks down glycogen

glycogenolysis).

Low-energy phosphates:

have G0′ values smaller than that of ATP. •ester phosphates found in the intermediates of glycolysis)

The creatine phosphate shuttle of

heart and skeletal muscle.

Catalase is a

hemoprotein containing four heme groups. •It can act as a peroxidase, •also able to catalyze the breakdown of H2O2 formed by the action of oxygenas

ROS are

highly reactive oxygen-containing molecules such as peroxides which are formed during normal metabolism, but can be damaging if they accumulate.

Examples include the liver enzymes:

homogentisate dioxygenase (oxidase) which contains iron •3-hydroxyanthranilate dioxygenase (oxidase) which contains iron •L-tryptophan dioxygenase (tryptophan pyrolase) which utilizes heme.

an endergonic process must be coupled in what system?

in an exergonic-endergonic system where the overall net change is exergonic.

All energy released from the oxidation of carbohydrate, fat, and protein is made available

in mitochondria as reducing equivalents (—H or e−). These are funneled into the respiratory chain, where they are passed down a redox gradient of carriers to their final reaction with oxygen to form water.

Creatine kinase m (CKm) is found

in the mitochondrial intermembrane space, catalyzing the transfer of high-energy phosphate to creatine from ATP emerging from the adenine nucleotide transporter.

Many drugs such as phenobarbital have the ability to

induce the synthesis of cytochromes P450.

MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke):

inherited condition due to NADH-Q oxidoreductase (Complex I) or cytochrome oxidase (Complex IV) deficiency. •It is caused by a mutation in mitochondrial DNA •may be involved in Alzheimer disease and diabetes mellitus.

The classic poisons H2S, carbon monoxide, and cyanide

inhibit Complex IV and can therefore totally arrest respiration.

A number of drugs and poisons act by

inhibition of oxidative phosphorylation

Atractyloside

inhibits oxidative phosphorylation by inhibiting the transporter of ADP into and ATP out of the mitochondrion

The redox carriers are grouped into four respiratory chain complexes in the_________. Three of the four complexes create an _______________between the _________and the

inner mitochondrial membrane, electrochemical potential, matrix, inner membrane space.

Most of the aerobic takes place

inside mitochondria, which have been termed the "powerhouses" of the cell.

causes the migration of these vesicles to the cell surface where they activate.

insulin

__________and___________: Control the formation and utilization of reserves of triacylglycerol and glycogen

insulin and glucagon

Enzymes, including adenylyl kinase and creatine kinase are found in the __________

intermembrane space.

As insulin secretion falls the receptors are

internalized again, reducing glucose uptake.

Malonate

is a competitive inhibitor of Complex II.

Cachexia

is an extreme wasting syndrome seen in chronic illness (cancer)

The electron-transferring flavoprotein (ETF)

is an intermediary carrier of electrons between acyl-CoA dehydrogenase and the respiratory chain

ΔH

is approximately equal to the total change in internal energy of the reaction or ΔE, so ΔG= ΔE-TΔS

the malate shuttle system (Figure 13-13)

is more complex but efficient (1:1 yield) and is found in liver, heart and kidney.

The outer membrane

is permeable to most metabolites and membrane is characterized by the presence of various enzymes, including acyl-CoA synthetase and glycerolphosphate acyltransferase

superoxide dismutase (SOD)

is responsible for its removal in all aerobic organisms (although not in obligate anaerobes), the potential toxicity of oxygen is due to its conversion to superoxide.

The inner membrane

is selectively permeable. The outer membrane is characterized by the presence of various enzymes, including acyl-CoA synthetase and glycerolphosphate acyltransferase.

Gibbs change in free energy (.G)

is that portion of the total energy change in a system that is available for doing work—that is, the useful energy, also known as the chemical potential.

Entropy (.S)

is the extent of disorder or randomness of the system and becomes maximum as equilibrium is approached.

When the reactants are 1.0 mol/L, what is ΔG0:

is the standard free-energy change

Lack of insulin results in increased lipolysis in adipose tissue, and ketogenesis in the liver. In uncontrolled diabetes, the ketosis may be severe enough to result in pronounced acidosis ;

ketoacidosis)

Those amino acids that give rise to acetyl-CoA are referred to as _________

ketogenic.

Acetyl-CoA is used to synthesize the ____________

ketone bodies

The brain can use _____________ to meet about 20% of its energy requirements; the remainder must be supplied by glucose.

ketone bodies

In tissues such as heart, metabolic fuels are oxidized in the following order of preference:

ketone bodies > fatty acids > glucose.

In the liver,Acetyl-CoA is used to form the________,________,_________which are important fuels in prolonged fasting and starvation.

ketone bodies, acetoacetate and 3-hydroxybutyrate

Partial oxidation of fatty acids in the liver leads to ____________production (___________-).

ketone body , ketogenesis

Alternative metabolic fuels (________________) are used for other tissues.

ketones

The high demand for glucose by the fetus, and for lactose synthesis in lactation, can lead to _____________.

ketosis

nucleoside monophosphate (NMP)

kinases catalyze the formation of nucleoside diphosphates from the corresponding monophosphates. Thus, adenylate kinase is a specialized NMP kinase.

Patients present with myopathy and encephalopathy and often have _____________

lactic acidosis. Several inherited defects of mitochondria involving components of the respiratory chain and oxidative phosphorylation have been reported.

The alanine, and the keto acids resulting from this transamination are exported to the ____________-, where alanine is transaminated to yield _____________.

liver, pyruvate

The liver also synthesizes the ____________- and ______________- that are in excess of requirements, synthesizing urea, which excreted via the kidney.

major plasma proteins (eg, albumin), deaminates amino acids

Peroxisomes are found in

many tissues, including liver.

The Mitochondrial___________ is enclosed by a double membrane

matrix

Substrate concentration is a factor in the control of the overall rate of a _______________.

metabolic pathway

the primary use of muscle glycogen is to provide for ___________in the ___________itself.

metabolism in the muscle

Erythrocytes lack_________-

mitochondria (can only do glycolysis).

Q and cytochrome c are.

mobile

xanthine oxidase, which contains_______________ and plays an important role in

molybdenum and plays an important role in the conversion of purine bases to uric acid.

One-way outcome makes these _______________. that are essentially irreversible.

non-equilibrium reactions

The ___________-or___________- are supplied in the diet, but can also be formed from ____________by transamination

nonessential or dispensable amino acids, metabolic intermediates

Heterotrophic organisms

obtain free energy by coupling their metabolism to the breakdown of complex organic molecules. •ATP plays a central role in the transference of free energy from the exergonic to the endergonic processes (as currency). •ATP is a nucleotide consisting of the nucleoside adenosine and three phosphate groups. •In its reactions in the cell, it functions as the Mg2+ complex.

Metalloflavoproteins contain

one or more metals as essential cofactors.

In a biochemical system, an enzyme does what

only speeds up the attainment of equilibrium; it never alters the final concentrations of the reactants at equilibrium. -actual ΔG may be larger or smaller than ΔG0 depending on conditions.

In gluconeogenesis, substrates such as lactate and pyruvate, which are formed in the cytosol, enter the mitochondrion, yield _____________ as a precursor for gluconeogenisis in the cytosol.

oxaloacetate

Superoxide can reduce

oxidized cytochrome c, or be removed by superoxide dismutase, which catalyzes the conversion of (O2-) to oxygen and hydrogen peroxide. In this reaction, superoxide acts as both oxidant and reductant.

1.As with acetyl-CoA arising from glycolysis, it is____________- to CO2 + H2O via the ____________.

oxidized, citric acid cycle

In the final step of cytochromes:

oxygen accepts the electrons from cytochrome P450 and is reduced, with one atom being incorporated into H2O and the other into the substrate, usually resulting in its hydroxylation. (hydroxylase cycle)

Oxidases catalyze the removal of hydrogen from a substrate using

oxygen as a hydrogen acceptor.∗ They form water or hydrogen peroxide as a reaction product.

Life is dependent upon a supply of

oxygen for respiration by which cells derive energy (ATP).

superoxide can be formed from

oxygen in tissues

For biochemical reactions, a standard state is defined as having a pH of what?

pH of 7.0.

the ____________ pathway, the source of_________ for nucleotide and nucleic acid synthesis.

pentose phosphate, ribose

Two type of enzymes fall into the hydroperoxidase category:

peroxidases and catalase.

Thermogenin (or the uncoupling protein) is a

physiological uncoupler found in brown adipose tissue that functions to generate body heat, particularly for the newborn and during hibernation in animals

Hydroperoxidases

play an important role in protecting the body against the harmful effects of reactive oxygen species (ROS).

The___________also occur naturally in foods. They are poorly absorbed, and have about half the energy yield of sugars.

polyhydric alcohols (sugar alcohols or polyols)

Transfer of an electron to O2 generates the

potentially damaging superoxide anion free radical ( O2-). Gives rise to free-radical chain reactions amplifying its destructive effects.

As fasting becomes prolonged, amino acids released as a result of _____________ are utilized in the liver and kidneys for _____________.

protein catabolism, gluconeogenesis

The ribosomes are responsible for .

protein synthesis

The electrochemical potential difference across the membrane, once established as a result of

proton translocation, inhibits further transport of reducing equivalents through the respiratory chain unless discharged by back-translocation of protons across the membrane through the ATP synthase. This in turn depends on availability of ADP and Pi.

The flow of electrons through Complexes I, III, and IV results in the

pumping of protons from the matrix across the inner mitochondrial membrane into the intermembrane space.

acetyl-CoA accumulates and inhibits______________-

pyruvate dehydrogenase.

Amino acids yield _________________of the citric acid cycle:

pyruvate, or intermediates

Group transfer potential,

rather than "high-energy bond," applies to bonded phosphates (~Ⓟ ). ATP contains two high-energy phosphate groups and ADP contains one, whereas the phosphate in AMP (adenosine monophosphate) is of the low-energy type since it is a normal ester link

In oxidation and reduction, the free energy changes as

reactants to donate or accept electrons.

Superoxide is formed when

reduced flavins—present, for example, in xanthine oxidase—are reoxidized univalently by molecular oxygen:

The respiratory chain collects and transports

reducing equivalents (electrons and protons), Reacting them with oxygen to form water.

The oxidation of carbohydrate, fatty acids, and amino acids within mitochondria yields____________

reducing equivalents (—H or electrons)

Malate shuttle for transfer of

reducing equivalents from the cytosol into the mitochondrion. α-Ketoglutarate transporter and glutamate/aspartate transporter (note the proton symport with glutamate).

The transfer of ___________ through the ______________ requires ___________, linked by ______________ on each side of the________________

reducing equivalents, mitochondrial membrane, substrate pairs, suitable dehydrogenases, mitochondrial membrane.

Oxidation of a molecule (electron donor) is accompanied by what

reduction of another (electron acceptor).

Oxidation:

removal of electrons.

Endergonic reactions

require the gain of free energy (ΔG is positive) and occur only when coupled to exergonic reactions.

ATP synthase spans the membrane and acts like a

rotary motor using the potential energy of the proton gradient or proton motive force to synthesize ATP from ADP and Pi.

glutathione peroxidase in RBCs, contains

selenium as a prosthetic group, catalyzes the destruction of H2O2 and lipid hydroperoxides through the conversion of reduced glutathione to its oxidized form, protecting membrane lipids and hemoglobin against oxidation by peroxides .

Oxidoreduction of isoalloxazine ring in flavin nucleotides via a

semiquinone intermediate

The fatty acids are transported bound to ____________; taken up by most tissues and either esterified to ___________- for storage or oxidized as a ________________.

serum albumin, triacylglycerols, fuel

Pyruvate has a

special carrier involving a symport that utilizes the H+ gradient (Figure 13-10).

Sites of inhibition ( -) of the respiratory chain by

specific drugs, chemicals, and antibiotics.(BAL, dimercaprol; TTFA, an Fe-chelating agent.

Dicarboxylate and tricarboxylate anions (eg, malate, citrate) and amino acids require

specific transporter or carrier systems to facilitate their passage across the membrane, linked to phosphate.

Phosphagens:

storage forms of high-energy phosphate; creatine phosphate and arginine phosphate, occurs in muscle. When the ATP/ADP ratio is high, their concentration can store of high-energy phosphate.

Tissue and organ level:

substrates entering and metabolites leaving can be measure

Barbiturates

such as amobarbital inhibit electron transport via Complex I by blocking the transfer from Fe-S to Q. At sufficient dosage, they are fatal in vivo

Oxygenases are concerned with the

synthesis or degradation of many different types of metabolites.

Exergonic reactions

take place spontaneously with loss of free energy (ΔG is negative

(3) Amphibolic pathways:

the "crossroads" of metabolism, acting as links between the anabolic and catabolic pathways, for example, the citric acid cycle.

ATP acts as

the "energy currency" of the cell, transferring free energy derived from substances of higher energy potential to those of lower energy potential.

Flavoproteins & Iron-Sulfur Proteins (Fe-S) Are Components of

the Respiratory Chain Complexes. These may contain one, two, or four Fe atoms linked to inorganic sulfur atoms and/or via cysteine-SH groups to the protein. The Fe-S take part in single electron transfer reactions in which one Fe atom undergoes oxido-reduction between Fe2+ and Fe3+.

Tissues exclusively dependent on glucose:

the brain & erythrocytes.

(2) Catabolic pathways:

the breakdown of larger molecules, commonly involving oxidative reactions; they are exothermic, producing reducing equivalents, and, mainly via the respiratory chain

The rate of detoxification of drugs by cytochromes P450 determines

the duration of their action.

2 shuttles for NADH reducing equivalent transfer exist in the mitochondrian:

the glycerophosphate shuttle is shown in Figure 13-12. This shuttle is present in some tissues (eg, brain, white muscle), looses 1 ATP (3:2 yield). •the malate shuttle system (Figure 13-13) is more complex but efficient (1:1 yield) and is found in liver, heart and kidney.

Oxidative phosphorylation:

the greatest quantitative source of ~Ⓟ in aerobic organisms. •ATP is generated in the mitochondrial matrix.

The four complexes are embedded in

the inner mitochondrial membrane

Metabolism:

the interconversion of chemical compounds, the pathways taken by individual molecules, their interrelationships, and the mechanisms that regulate the flow of metabolites. Metabolic pathways fall into three categories.

the first reaction of glycolysis:

the phosphorylation of glucose to glucose-6-phosphate. Endergonic reactions cannot proceed without an input of free energy.

Gluconeogenesis is

the process of synthesizing glucose from non-carbohydrate precursors such as, lactate, amino acids, and glycerol

-ΔG

the reaction is spontaneous with loss of free energy and exergonic. If, ΔG is great the reaction goes virtually to completion and is essentially irreversible.

+ΔG :

the reaction proceeds only if free energy can be gained and is endergonic. If ΔG is great, the system is stable, with little or no tendency for a reaction to occur.

3.Pyranose and furanose ring structures:

the ring structures of monosaccharides are similar to the ring structures of either pyran (a six-membered ring) or furan (a five-membered ring) (Figures 15-3 and 15-4). For glucose in solution, more than 99% is in the pyranose form.

Bioenergetics (biochemical thermodynamics):

the study of the energy changes accompanying biochemical reactions

(1) Anabolic pathways:

the synthesis of larger and more complex compounds from smaller precursors.

If ΔG is zero,

the system is at equilibrium and no net change takes place.

1st law of thermodynamics:

the total energy of a system, including its surroundings, remains constant. -energy is neither lost nor gained during any change. -energy may be transferred from one part of the system to another or transformed into another form of energy. -chemical energy may be transformed into heat, electrical, radiant, or mechanical energy.

2nd law of thermodynamics:

the total entropy of a system must increase if a process is to occur spontaneously. -Entropy (.S)

High-energy phosphates

the value is higher than that of ATP. The components of this latter group, including ATP, are usually •anhydrides (eg, the 1-phosphate of 1,3-bisphosphoglycerate), •enolphosphates (eg, phosphoenolpyruvate), •phosphoguanidines (eg, creatine phosphate, arginine phosphate).

•FMN and FAD are usually tightly—but not covalently—bound to

their respective apoenzyme proteins.

NAD+ and NADP+ are able to freely and reversibly dissociate from

their respective apoenzymes.

Flavin groups are generally more_____________ than are the nicotinamide coenzymes.

tightly bound to their apoenzymes

Pyruvate builds up and is transaminated to

to alanine

Oxidation-reduction applies to what

to biochemical systems and is important in understanding biologic oxidation.

The creatine phosphate shuttle:

transfers of high-energy phosphate from mitochondria to cytoplasm in active tissues such as heart and skeletal muscle.

Many Monosaccharides Are Physiologically Important Derivatives of _______,________,______,______ are formed as metabolic intermediates in _____and_________ Pentoses are important in______,_____,_______ _____,_______,________,_______are physiologically the most important hexoses. The biochemically important ketoses are shown in Figure 15-6, and aldoses in Figure 15-7.

trioses, tetroses, and pentoses and sedoheptulose, glycolysis and the pentose phosphate pathway. nucleotides, nucleic acids, and several coenzymes) . Glucose, galactose, fructose, and mannose .

The oxidized flavin nucleotide (FMN or FAD) can be reduced in reactions involving the transfer of

two electrons (to form FMNH2 or FADH2), but they can also accept one electron to form the semi-quinone

This transfer of four electrons from cytochrome c to O2 involves

two heme groups, a and a3, and Cu

In _______________, patients may become hyperglycemic, from lack of insulin to stimulate uptake and utilization of glucose, and the absence of insulin to antagonize the actions of glucagon.

type 1 diabetes mellitus

The IMMis freely permeable to

uncharged small molecules, such as oxygen, water, CO2, NH3, and monocarboxylic acids (3-hydroxybutyric, acetoacetic, and acetic), in their undissociated, form. Long-chain fatty acids are transported into mitochondria via the carnitine system.

Catalase process

uses one H2O2 as electron donor and another H2O2 as electron acceptor. •It is one of the fastest enzyme reactions known. •Under most conditions in vivo, the peroxidase activity of catalase seems to be favored. •Catalase is found in blood, bone marrow, mucous membranes, kidney, and liver.

Autotrophic organisms

utilize simple exergonic processes; eg, the energy of sunlight (green plants), the reaction Fe2+ → Fe3+ (some bacteria).

Identified as a non-equilibrium reaction in which the Km of the enzyme is ___________.

very low,

Nicotinamide Adenine Dinucleotide (NAD+) or Nicotinamide Adenine Dinucleotide Phosphate (NADP+) formed in the body from the __________

vitamin niacin. The oxidized forms of both nucleotides have a positive charge on the nitrogen atom of the nicotinamide moiety as indicated.

FMN and FAD formed the

vitamin riboflavin.

anabolism

whereas the synthetic reactions that build up substances

The standard free-energy change at this standard state is denoted by______?

ΔG0′

what is the equation that combines the two laws of thermodynamics: at constant temperature and pressure.

ΔG= ΔH-TΔS where ΔH is the change in enthalpy (heat) and T is the absolute temperature.

standard free-energy change equation

ΔGo'= -RT ln Keq' R is the gas constant T is the absolute temperature

Oxygenases catalyze the incorporation of oxygen into a substrate molecule in two steps:

•(1) oxygen is bound to the enzyme at the active site •(2) the bound oxygen is reduced or transferred to the substrate.

P450 enzymes include:

•Biosynthesis of steroid hormones from cholesterol (hydroxylation at C22 and C20 in side-chain cleavage and at the 11β and 18 positions). •Renal 1α- and 24-hydroxylations of 25-hydroxycholecalciferol in vitamin D metabolism— •Cholesterol 7α-hydroxylase and sterol 27-hydroxylase i in bile acid biosynthesis in the liver.

DEHYDROGENASES: They perform the what two main functions:

•Transfer of hydrogen from one substrate to another in a coupled oxidation-reduction reaction •These dehydrogenases are specific for their substrates utilize NAD+ or FAD+. (Figure 12-3). •are reversible, enable reducing equivalents to be freely transferred within the cell. •enables one substrate to be oxidized at the expense of another •enabling oxidative processes to occur in the absence of oxygen, (anaerobic phase of glycolysis) Transfer of electrons in the respiratory chain of electron transport from substrate to oxygen (see Figure 13-3.

Mitochondrial cytochrome P450 systems are found in steroidogenic tissues:

•adrenal cortex, •testis •ovary •placenta

Cytochrome oxidase

•terminal component of the respiratory chain of mitochondria •transfers electrons to oxygen. •blocked by carbon monoxide, cyanide, and hydrogen sulfide. •It has also been termed "cytochrome a3." •contains two molecules of heme, two Fe (Fe3+ and Fe2+ during oxidation and reduction). •two atoms of Cu are present, each associated with a heme unit. ∗The term "oxidase" is sometimes used collectively to denote all enzymes that catalyze reactions involving molecular oxygen.

The endoplasmic reticulum membranes contain the enzyme system for

•triacylglycerol synthesis

Transporter systems in the inner mitochondrial membrane.

➀ Phosphate transporter, ➁ pyruvate symport, ➂ dicarboxylate transporter, ➃ tricarboxylate transporter, ➄ α-ketoglutarate transporter, ➅ adenine nucleotide transporter. N-Ethylmaleimide, hydroxycinnamate, and atractyloside inhibit ( ) the indicated systems. Also present (but not shown) are transporter systems for glutamate/aspartate (Figure 13-13), glutamine, ornithine, neutral amino acids, and carnitine

Mechanisms of control of an enzyme-catalyzed reaction.

➀ alteration of membrane permeability; ➁ conversion of an inactive to an active enzyme, usually involving phosphorylation/dephosphorylation reactions; ➂ alteration of the rate translation of mRNA at the ribosomal level; ➃ induction of new mRNA formation; and ➄ repression of mRNA formation. ➀ and ➁ are rapid, whereas ➂, ➃, and ➄ are slower mechanisms of regulation