BIL 255 Chapter 13 review

regulation of metabolism

A cell is an intricate chemical machine and our discussion of metabolism - with a focus of glycolysis and the citric acid cycle - has considered only a tiny fraction of the many enzymatic reactions that can take place in a cell at any time For all these pathways to work together smoothly, as is required to allow the cell to survive and to respond to tis environment, the choice of which pathway each metabolite will follow must be carefully regulated at every branch point

origin of citric acid cycle

Although living organisms have inhabited Earth for the past 3.5 billion years, the planet is thought to have developed an atmosphere containing O2 gas only some 1 to 2 billion years ago Many of the energy generating reactions of the citric acid cycle - also called the tricarboxylic acid cycle or the krebs cycle - are therefore likely to be of relatively recent origin

problem to maintain order within their cells, all organisms need to replenish their ATP pools continuously through the oxidation of sugars or fats Yet the animals have only periodic access to food and plants need to survive without sunlight overnight, when they are unable to produce sugar through photosynthesis

Animals and plants have evolved several ways to cope with this problem One way is to synthesize food reserves in times of plenty that can be later consumed when other energy sources are scarce Thus, depending on conditions, a cell must decide whether to route key metabolites into anabolic or catabolic pathways - in other words, whether to use them to build other molecules or burn them to provide immediate energy

at the end of the ETC electrons and O2

At the end of the transport chain, the electrons are added to molecules of O2 that have diffused into the mitochondria and the resulting reduced oxygen molecules immediately combine with protons from the surrounding solution to produce water The electrons have now reached their lowest energy level, with all the available energy extracted from the food molecule being oxidized

products of pyruvate decarboxylation

CO2 (a waste product), NADH, and acetyl CoA

process of oxidative phosphorylation

During oxidative phosphorylation, NADH and FADH2 transfer their high energy electrons to the electron transport chain - a series of electron carriers embedded in the inner mitochondrial membrane in eukaryotic cells and in the plasma membrane of aerobic bacteria As the electrons pass through the series of electron acceptor and donor molecules that form the chain, they fail to successively lower energy states At specific sites in the chain, the energy released is used to drive H+ (protons) across the inner membrane from the mitochondrial matrix to the intermembrane space This movement generates a proton gradient across the inner membrane which serves as a source of energy that can be tapped to drive a vareity of energy requiring reactions The most prominent of these reactions is the phosphorylation of ADP to generate ATP on the matrix side of the inner membrane

coordination and regulation of glycogen synthetic and degradative pathways

Enzymes in each pathway are allosterically regulated by glucose 6 phosphate but in opposite directions: glycogen synthetase in the synthetic pathway is activated by glucose 6 phosphate, whereas glycogen phosphorylase, which breaks down glycogen, is inhibited by glucose 6 phosphate as well as by ATP This regulation helps to prevent glycogen breakdown when ATP is plentiful and to favor glycogen synthesis when glucose 6 phosphate concentration is high The balance between glycogen synthesis and breakdown is further regulated by intracellular signaling pathways that are controlled by the hormones insulin, adrenaline and glucagon

anaerobic conditions fermentation

In these anaerobic conditions, the pyruvate and NADH made by glycolysis remain in the cytosol The pyruvate is converted into products that are excreted from the cell: lactate in muscle cells or ethanol and CO2 in yeast cells used in brewing and breadmaking The NADH gives up its electrons in the cytosol and is converted back to the NAD+ required to maintain the reactions of glycolysis Such energy yielding pathways that break down sugar in the absence of oxygen are called fermentations Scientific studies of the commercially important fermentations carried out by yeasts laid the foundations for early biochemistry

products of fatty acids in glycolysis and acetyl CoA formation

Fatty acids are first activated by covalent linkage to CoA and are then broken down completely by a cycle of reactions that trims two carbons at a time from their carboxyl end, generating one molecule of acetyl CoA for each turn of the cycle Two activated carriers - NADH and another high energy electron carrier - FADH2, are also produced in this process

2 ways in which animals make ATP

First, certain energetically favorable enzyme catalyzed reactions involved in the breakdown of foods are directly coupled to the energetically unfavorable reaction ADP + Pi = ATP Thus the oxidation of food molecules can provide energy for the immediate production of ATP Most ATP synthesis however requires an intermediary In this second pathway to making ATP, energy from other activated carriers is used to drive ATP production This process is called oxidative phosphorylation, takes place in the inner mitochondrial membrane and is described in detail later

glycogen - why is isn't as important as fat

Glycogen binds a great deal of water, producing a sixfold difference in the actual mass of glycogen required to store the same amount of energy as fat An average adult human stores enough glycogen for only about a day of normal activity, but enough fat to last nearly a month If our main fuel reserves had to be carried as glycogen instead of fat, body weight would need to be increased by an average of about 60 pounds

amino acids and glycolysis

In addition to pyruvate and fatty acids, some amino acids are transported from the cytosol into the mitochondrial matrix, where they are also converted into acetyl CoA or one of the other intermediates of the citric acid cycle

activated carriers produced by citric acid cycle

In addition to three molecules of NADH, each turn of the cycle also produces one molecule of FADH2 and one molecule of GTP from GDP The structures of these two activated carriers are shown below GTP is a close relative of ATP and the transfer of its terminal phosphate group to ADP produces one ATP molecule in each cycle Like NADH, FADH2 is a carrier of high energy electrons and hydrogen

misconception about citric acid cycle atmospheric O2 molecule required for the process to proceed is converted into the CO2 that is released as a waste product

In fact, the oxygen atoms required to make CO2 from the acetyl groups entering the citric acid cycle are supplied not by O2 but by water Three molecules of water are split in each cycle and the oxygen atoms of some of them are ultimately used to make CO2 The O2 that we breathe is actually reduced to water by the electron transport chain; it is not incorporated directly into the CO2 we exhale

when are fatty acids released from adipocytes?

In response to hormonal signals, fatty acids can be released from these depots into the bloodstream for other cells to use as required Such a need arises after a period of not eating

anaerobic respiration

Many bacteria and archaea can also generate ATP in the absence of oxygen by anaerobic respiration, a process that uses a molecule other than oxygen as a final electron acceptor Anaerobic respiration differs from fermentation in that it involves an electron transport chain embedded in a membrane - plasma membrane

energy from breakdown of glucose vs a modern combustion engine

In total, nearly half of the energy that could, in theory, be derived from the breakdown of glucose or fatty acids to H2O and CO2 is captured and used to drive the energetically unfavorable reaction ADP + Pi = ATP By contrast, a modern combustion engine, such as a car engine, can convert no more than 20% of the available energy in fuel into useful work In both cases, the remaining energy is released as heat, which in animals helps to keep the animal warm

amount of ATP produced in glycolysis vs oxidative phosphorylation

In total, the complete oxidation of a molecule of glucose to H2O and CO2 can produce about 30 molecules of ATP In contrast, only two molecules of ATP are produced per molecule of glucose by glycolysis alone

substrate level phosphorylation

Much of the energy released by the breakdown of glucose is used to drive the synthesis of ATP molecules from ADP and Pi This form of ATP synthesis, which takes place in steps 7 and 10 in glycolysis, is known as substrate level phosphorylation because it occurs by the transfer of a phosphate group directly from a substrate molecule - one of the sugar intermediates to ADP By contrast, most phosphorylations in cells occur by the transfer of phosphate from ATP to a substrate molecule

molecules of NADH and NAD+

Over the course of glycolysis, two molecules of NADH are formed per molecule of glucose In aerobic organisms, these NADH molecules donate their electrons to the electron transport chain in the inner mitochondrial membrane Such electron transfers release energy as the electrons fall from a state of higher energy to a lower one The electrons that are passed along the electron transport chain are ultimately passed on to O2, forming water In giving up its electrons, NADH is converted by to NAD+, which is then available to be used again for glycolysis In the absence of oxygen, NAD+ can be regenerated by an alternate type of energy yielding reaction called a fermentation

major triumph of piecing together the complete glycolytic pathway

Piecing together the complete glycolytic pathway in the 1930s was a major triumph of biochemistry, as the pathway consists of a sequence of 10 separate reactions, each producing a different sugar intermediate and each catalyzed by a different enzyme

food reserves in animals and plants

Plants convert some of the sugars they make through photosynthesis during daylight into fats and into starch, a branched polymer of glucose very similar to animal glycogen The fats in plants are triacylglycerols and they differ only in the types of fatty acids that predominate

plants and animals sugar

Plants make their own sugars from CO2 by photosynthesis Animals obtain sugars - and other organic molecules that can be chemically transformed into sugars - by eating plants and other organisms

how many ATP are in a cell?

Roughly 10^9 molecules of ATP are in solution in a typical cell at any instant In many cells, all of this ATP is turned over (that is, consumed and replaced) every 1-2 minutes An average person at rest will hydrolyze his or her weight in ATP molecules every 24 hours

energetic costs of gluconeogenesis

Some of the biosynthetic bypass reactions required for gluconeogenesis are energetically costly Production of a single molecule of glucose by gluconeogenesis consumes four molecules of ATP and two molecules of GTP Thus a cell must tightly regulate the balance between glycolysis and gluconeogenesis

regulation of phosphofructokinase

The activity of the enzyme phosphofructokinase is allosterically regulated by the binding of a variety of metabolites, which provide both positive and negative feedback regulation The enzyme is activated by byproducts of ATP hydrolysis - including ADP, AMP and inorganic phosphate and it is inhibited by ATP Thus, when ATP is depleted and its metabolic byproducts accumulate, phosphofructokinase is turned on and glycolysis proceeds to generate ATP; when ATP is abundant, the enzyme is turned off and glycolysis shuts down The enzyme that catalyzes the reverse reaction, fructose 1,6 bisphosphatase is regulated by the same molecules but in the opposite direction Thus this enzyme is activated when phosphofructokinase is turned off, allowing gluconeogenesis to proceed

what occurs in the citric acid cycle?

The citric acid cycle catalyzes the complete oxidation of the carbon atoms of the acetyl groups in acetyl CoA, converting them into CO2 The acetyl group is not oxidized directly, however Instead, it is transferred from acetyl CoA to a larger four carbon molecule, oxaloacetate, to form the six carbon tricarboxylic acid, citric acid, for which the subsequent cycle of reactions is named The citric acid molecule is then progressively oxidized, and the energy of this oxidation is harnessed to produce activated carriers in much the same manner The chain of eight reactions forms a cycle, because the oxaloacetate that began the process is regenerated at the end The citric acid cycle is presented in detail

citric acid O2 - yes or no?

The citric acid cycle, which takes place in the mitochondrial matrix, does not itself use O2 However, it requires O2 to proceed because the electron transport chain - which uses O2 as its final acceptor - allows NADH to get rid of its electrons and thus regenerate the NADP+ needed to keep the cycle going

embryo with plant seeds stored food reservoirs

The embryo inside a plant seed must live on stored food reservoirs for a long time, until the seed germinates to produce a plant with leaves that can harvest the energy in sunlight The embryo uses these food stores as sources of energy and of small molecules to build cell walls and to synthesize many other biological molecules as it develops For this reason, plant seeds often contain especially large amounts of fats and starch - which make them a major food source for animals, including ourselves Germinating seeds convert the stored fat and starch into glucose as needed

energy from NADH and FADH2

The energy stored in the readily transferred high energy electrons of NADH and FADH2 is subsequently used to produce ATP through oxidative phosphorylation on the inner mitochondrial membrane, the only step in the oxidative catabolism of foodstuffs that directly requires O2 from the atmosphere

reaction of glyceraldehyde 3 phosphate to 3 phosphglycerate releases

The overall reaction releases enough free energy to transfer two electrons from the aldehyde to NAD+ to form NADH and to transfer a phosphate group to a molecule of ADP to form ATP It also releases enough heat to the environment to make the overall reaction energetically favorable: the delta G for step 6 followed by step 7 is -3.0 kcal/mol

breakdown of molecules

The proteins, fats and polysaccharides that make up most of the food we eat must be broken down into smaller molecules before our cells can use them - either as a source of energy or as building blocks for making other organic molecules

conversion of glyceraldehyde 3 phosphate to 3 phosphglycerate

The reactions in question convert the three carbon sugar intermediate glyceraldehyde 3 phosphate (an aldehyde) into 3 phosphoglycerate (a carboxylic acid) This conversion, which entails the oxidation of an aldehyde group to a carboxylic acid group, occurs in two steps

oxidative phosphorylation

The remainder of the energy released during glycolysis is stored in the electrons in the NADH molecule produced in step 6 by an oxidative reaction Oxidation does not always involve oxygen; it occurs in any reaction in which electrons are lost from one atom and transferred to another Although no molecular oxygen is involved in glycolysis, oxidation does occur: in step 6, a hydrogen atom plus an electron is removed from the sugar intermediate, glyceraldehyde 3 phosphate and transferred to NAD+, producing NADH

how does gluconeogenesis get around one-way steps of glycolysis?

To get around these one way steps, gluconeogenesis uses a special set of enzymes to catalyze a set of bypass reactions In step 3 of glycolysis, the enzyme phosphofructokinase catalyzes the phosphorylation of fructose 6 phosphate to produce the intermediate fructose 1,6 biphosphate In gluconeogenesis, the enzyme fructose 1,6 bisphosphatase removes a phosphate from this intermediate to produce fructose 6 phosphate

stage 1 of catabolism

enzymes convert the large polymeric molecules in food into simpler monomeric subunits: proteins into amino acids, polysaccharides into sugars, and fats into fatty acids and glycerol This stage, also called digestion, occurs either outside cells (in the intestine) or in specialized organelles within cells called lysosomes After digestion, the small organic molecules derived from food enter the cytosol of a cell, where their gradual oxidative breakdown begins

stage 2 of catabolism

a chain of reactions called glycolysis splits each molecule of glucose into two smaller molecules of pyruvate Sugars other than glucose can also be used, after first being converted into one of the intermediates in this sugar splitting pathway Glycolysis takes place in the cytosol and in addition to producing pyruvate, it generates two types of activated carriers: ATP and NADH The pyruvate is transported from the cytosol into the mitochondrion's large, internal compartment called the matrix There, a giant enzyme complex converts each pyruvate molecule into CO2 plus acetyl CoA, another of the activated carriers In the same compartment, large amounts of acetyl CoA are also produced by the stepwise oxidative breakdown of fatty acids derived from fats

cells require

a constant supply of energy to generate and maintain the biological order that allows them to grow, divide, and carry out their day to day activities

fat and glycolysis

a major source of energy for most non photosynthetic organisms, including humans Like the pyruvate derived from glycolysis, the fatty acids derived from fat are also converted into acetyl CoA in the mitochondrial matrix Fatty acids are first activated by covalent linkage to CoA and are then broken down completely by a cycle of reactions that trims two carbons at a time from their carboxyl end, generating one molecule of acetyl CoA for each turn of the cycle

fatty acids vs glucose at meal times

a normal overnight fast results in the mobilization of fat: in the morning, most of the acetyl CoA that enters the citric acid cycle is derived from fatty acids rather than from glucose After a meal, however, most of the acetyl CoA entering the citric acid cycle comes from glucose derived from food and any excess glucose is used to make glycogen or fat

negative regulation

a repressor protein binds to an operator to prevent a gene from being expressed

gluconeogenesis

a reversal of glycolysis: it builds glucose from pyruvate, whereas glycolysis does the opposite Gluconeogenesis makes use of many of the same enzymes as glycolysis; it simply runs them in reverse

pyruvate

a substrate for half a dozen or more different enzymes, each of which modifies it chemically in a different way

positive regulation

a transcription factor is required to bind at the promoter in order to enable RNA polymerase to initiate transcription

citric acid cycle oxidation in carbon compounds

accounts for about two thirds of the total oxidation of carbon compounds in most cells

pyruvate and aerobic metabolism

actively pumped into the mitochondrial matrix There, it is rapidly decarboxylated by a giant complex of three enzymes, called the pyruvate dehydrogenase complex

enzymes that catalyze glycolysis

all have names ending in -ase, like isomerase and dehydrogenase - which specify the type of reaction they catalyze

feedback regulation

allows cells to switch from glucose breakdown to glucose synthesis

If a fuel molecule such as glucose were oxidized to CO2 and H2O in a single step, ex by fire, it would release

an amount of energy many times larger than any carrier molecule could capture

animals need

an ample supply of glucose Active muscles need glucose to power their contraction and brain cells depend almost completely on glucose for energy During periods of fasting or intense physical energy, the body's glucose reserves get used up faster than they can be replenished from food

To balance the activities of these interrelated reactions and to allow organisms to adapt swiftly to changes in food availability or energy expenditure . . .

an elaborate network of control mechanisms regulates and coordinates the activity of the enzymes that catalyze the myriad metabolic reactions that go on in a cell

paddle wheel analogy

explained how cells harvest useful energy from the oxidation of organic molecules by coupling an energetically unfavorable reaction to an energetically favorable one

energy contained in phosphate bonds

can be determined by measuring the standard free energy change when that bond is broken by hydrolysis

when more ATP is needed than can be generated from food molecules. . . .

cells break down glycogen in a reaction that is catalyzed by the enzyme glycogen phosphorylase This enzyme produces glucose 1-phosphate which is then converted to the glucose 6 phosphate that feeds into the glycolytic pathway

enzymes and breakdown of sugar

cells use enzymes to carry out the oxidation of sugars in a tightly controlled series of reactions Thanks to the action of enzymes - which operate at temperatures typical of living things - cells degrade each glucose molecule step by step, paying out energy in small packets to activated carriers by means of coupled reactions In this way, much of the energy released by the breakdown of glucose is saved in the high energy bonds of ATP and other activated carriers, which can then be made available to do useful work for the cell

how does a cell decide whether to synthesize glucose or degrade it?

centers on the reactions

energy comes from

chemical bond energy in food molecules, which thereby serve as fuel for cells

fat and starch are both stored in _____ in plant cells

chloroplasts

name of glycolysis

comes from the greek glykys and lysis, sweet and splitting It is an appropriate name, as glycolysis splits a molecule of glucose, which has six carbon atoms, to form two molecules of pyruvate, each of which contains three carbon atoms

positive and negative regulation

control the activity of key enzymes involved in the breakdown and synthesis of glucose

pyruvate dehydrogenase complex

converts pyruvate to acetyl CoA

lactate dehydrogenase

converts pyruvate to lactate during fermentation

enzymes allow

coupled reactions to facilitate the transfer of chemical energy to ATP and NADH

high energy chemical bonds

covalent bonds that release large amounts of energy when hydrolyzed

activity of enzymes can be controlled by

covalent modification such as the addition or removal of a phosphate group and by the binding of small regulatory molecules, often a metabolite

storage of fat

droplets of water insoluble triacylglycerols in specialized fat cells called adipocytes

anaerobic microorganisms

for many anaerobic microorganisms, which can grow and divide in the absence of oxygen, glycolysis is the primary source of ATP The same is true for certain animal cells, such as skeletal muscle cells, which can continue to function at low levels of oxygen

breakdown of glucose

generates most of the energy produced in the majority of animal cells

storage of food molecules in special reservoirs to prepare for times of need

gluconeogenesis is a costly process, requiring substantial amounts of energy from the hydrolysis of ATP and GTP During periods when food is scarce, this expensive way of producing glucose is suppressed if alternatives are available Thus fasting cells can mobilize glucose that has been stored in the form of glycogen, a branched polymer of glucose This large polysaccharide is stored as small granules in the cytoplasm of many animal cells, but mainly in liver and muscle cells

aerobic bacteria - have no mitochondria

glycolysis and acetyl CoA production, as well as the citric acid cycle, take place in the cytosol

high energy phosphate bonds

hydrolysis is particularly energetically favorable

substrate level phosphorylation

in the cytosol and mitochondrial matrix produce both ATP and the additional activated carriers that will subsequently help drive the production of much larger amounts of ATP by oxidative phosphorylation

glycolysis is only a prelude to the third and final stage of the breakdown of food molecules, in which

in which large amounts of ATP are generated in mitochondria by oxidative phosphorylation, a process that requires the consumption of oxygen

many intermediates are siphoned off by anabolic pathways

in which they are converted by a series of enzyme catalyzed reactions into amino acids, nucleotides, lipids and other small organic molecules that the cell needs

investment of energy of glucose pay-off phase

initial consumption of ATP to provide energy needed to prepare the sugar to be split more than recouped in the later steps of glycolysis, when four molecules of ATP are produced Energy is also captured in this "payoff phase" in the form of NADH

citric acid cycle major end products

major end products at CO2 and high energy electrons in the form of NADH The CO2 is released as a waste product while the high energy electrons from NADH are passed to the electron transport chain the inner mitochondrial membrane At the end of the chain, these electrons combine with O2 to produce H2O

oxidative phosphorylation

occurs in both eukaryotic cells and in aerobic bacteria It represents a remarkable evolutionary achievement and the ability to extract energy from food with such great efficiency has shaped the entire character of life on earth

oxidative phosphorylation

occurs in the inner mitochondrial membrane

why is fat more important?

oxidation of a gram of fat releases about twice as much energy as the oxidation of a gram of glycogen

evolution of glycolysis

probably evolved early in the history of life on earth, before photosynthetic organisms introduced oxygen into the atmosphere

catabolism

process in which enzymes degrade complex organic molecules into simpler ones three stages

catabolic reactions

produce both energy for the cell and the building blocks from which many other organic molecules are made

molecules that contain phosphate bonds that have more energy than those found in ATP

readily transfer their phosphate group to ADP to form ATP

energy derived from the breakdown of sugars and fats is

redistributed into packets of chemical energy in a form convenient for use in the cell

chloroplasts

specialized organelles that carry out photosynthesis these energy rich molecules serve as food reservoirs that are mobilized by the cell to produce ATP in mitochondria during periods of darkness

most important fuel molecules

sugars

way to increase available glucose

synthesize it from pyruvate by a process called gluconeogenesis

stage 3 of catabolism

takes place entirely in mitochondria The acetyl group of acetyl CoA is transferred to an oxaloacetate molecule to form citrate, which enters a series of reactions called the citric acid cycle In these reactions, the transferred acetyl group is oxidized to CO2 with the production of large amounts of NADH Finally, the high energy electrons from NADH are passed along a series of enzymes within the mitochondrial inner membrane called an electron transport chain, where the energy released by their transfer is used to drive oxidative phosphorylation - a process that produces ATP and consumes molecular oxygen It is in these final steps of catabolism that the majority of the energy released by oxidation is harnessed to produce most of the cell's ATP

citric acid cycle

the acetyl group in acetyl CoA is oxidized to CO2 and H2O in the mitochondrial matrix

mitochondrion

the center toward which all energy yielding catabolic processes lead, whether they begin with sugars, fats, or proteins

oxidative phosphorylation

the chemical energy captured by the activated carriers produced during glycolysis and the citric acid cycle is used to generate ATP

reaction in step 6

the only one in glycolysis that creates a high energy phosphate linkage directly from inorganic phosphate - substrate level phosphorylation

glycolysis

the oxidative breakdown of glucose in the sequence of reactions known as glycolysis Glycolysis produces ATP without the involvement of oxygen It occurs in the cytosol of most cells, including many anaerobic microorganisms that thrive in the absence of oxygen

breakdown of sugars in animals and plants

the process whereby all these sugars are broken down to generate energy is very similar in both animals and plants In both cases, the organism's cells harvest useful energy from the chemical bond energy locked in sugars as the sugar molecule is broken down and oxidized to carbon dioxide and water - a process called cell respiration The energy released during these reactions is captured in the form of "high energy" chemical bonds - covalent bonds that release large amounts of energy when hydrolyzed - in activated carriers such as ATP and NADH These carriers in turn serve as portable sources of chemical groups and electrons needed for biosynthesis

gain of molecules at end of glycolysis

there is a net gain of two molecules of ATP and two molecules of NADH for each glucose molecule broken down

although animal cells can readily convert sugars to fats . . .

they cannot convert fatty acids to sugars

The series of chemical rearrangements that ultimately generate pyruvate release energy because the electrons in a molecule of pyruvate, overall, are at a lower energy state than

those in a molecule of glucose

anabolic pathways oxaloacetate and alpha ketoglutarate

transferred from the mitochondrial matrix back to the cytosol, where they serve as precursors for the production of many essential molecules, such as amino acids aspartate and glutamate

For each molecule of glucose that enters glycolysis

two molecules of ATP are initially consumed to provide the energy needed to prepare the sugar to be split

electrons passed along the electron transport chain are

ultimately passed on to O2, forming water