BioChem 2

The Pentose Phosphate Pathway (PPP) OXIDATIVE PHASE equation: NADPH is used to, 2 things:

- Glucose-6-P → 6-Phosphogluconate → Ribulose-5-P - 1) reduce glutathione disulfide (GSSH) to glutathione (2GSH) and 2) act as a cofactor for reductive biosynthesis

Consumption of ATP Phosphorylation using ATP = Many enzymes, proteins, and signaling molecules are turned "on" or "off" by? ATP acts as?

- Major Human Body Regulatory Mechanism - the process of phosphorylation via a phosphoryl group transfer - the donor of the phosphate group needed for phosphorylation

1) The citric acid cycle is tightly regulated, because? 2) The pyruvate dehydrogenase complex, the entry point to the CAC, is inhibited by? 3) Pyruvate dehydrogenase is also inhibited by? 4) When NADH and ATP are low, pyruvate dehydrogenase is? 5) The citric acid cycle itself is regulated at many points. Isocitrate dehydrogenase is stimulated by? and inhibited by? 6) α-ketoglutarate dehydrogenase is inhibited by?

1) because without regulation, large amounts of NADH and ATP could be wasted. 2) its products, acetyl CoA and NADH. 3) phosphorylation stimulated by high levels of NADH and ATP. 4) dephosphorylated and activated. 5) ADP and inhibited by ATP and NADH. 6) its products, succinyl CoA and NADH, and is also inhibited by ATP

How many NADPH are produced per glucose-6-P molecule by the PPP? How many glutathione molecules are produced per glucose-6-P?

For each glucose 6-phosphate, TWO NADPH molecules are generated. Both come from the first reaction, glucose 6-phosphate converting to ribulose 5-phosphate. The pentose phosphate pathway does not directly generate glutathione molecules. However, the NADPH generated in the PPP can be used to reduce the oxidized form of glutathione to protect the cell from reactive oxygen species. To regenerate glutathione, the reaction is 1 glutathione disulfide + NADPH → 2 glutathione + NADP+. This means that for each glucose 6-phosphate, FOUR glutathiones are generated, because two NADPHs are generated

ΔG°' = Show how the above reaction is derived from ΔG = ΔG°'+ RTlnQ. Explain or justify each algebraic step conceptually

- -RTlnKeq - At equilibrium, Q = Keq and ΔG = 0. Starting with ΔG = ΔG°' + RTlnQ we have ΔG = ΔG°' + RTlnKeq and then 0 = ΔG°' + RTlnKeq. Subtracting RTlnKeq from both sides, we get ΔG°' = -RTlnKeq

-Oxidation REQUIRES (per 2-carbon cycle): ? Note: An activated fatty acid will already have an -S-CoA group on? The CoA-SH required here is added to?

- 1 FAD, 1 H2O, 1 NAD+ and 1 CoA-SH - the carbonyl end of the chain. - the 2-carbon acetyl group that is the product of the oxidation, creating an Acetyl-CoA rather than acetic acid)

β-Oxidation of Fatty Acids: NET RESULTS: Each 2-carbon cycle of β-oxidation yields:? ODD # of CARBONS: Fatty acids with an odd number of carbons will result in? This reacts via multiple steps to form succinyl-CoA which is then fed back into? You do NOT need to memorize these names, just remember that with odd-chain fatty acids there is?

- 1 FADH2 (2 ATP), 1 NADH (3 ATP) and 1 Acetyl-CoA (12 ATP). - a 3-carbon residue, propionyl-CoA. - the Krebs Cycle. - a leftover residue.

Redraw a simplified glycolysis chart and demonstrate the alternative pathways used to accomplish gluconeogenesis. Identify any enzymes that are NOT part of glycolysis

- 1) Glucose 6-phosphotase: conversion of Glucose 6-phosphotase to Glucose. 2) Fructose 1,6-biphosphotase: conversion of Fructose 1,6-biphosphotase to Fructose 6-phosphate. 3) Phosphoenolpyruvate carboxylkinase: conversion of oxaloacetate to phosphoenolpyruvate. 4) Pyruvate carboxylase: conversion to oxaloacetate

Complex I pumps how many protons? Complex II pumps? why? Complex III pumps? Complex IV? Utilizing electrons from an NADH molecule will result in how many protons pumped? why? Utilizing electrons from an FADH2 molecule will result in how many protons pumped? why? To generate one ATP molecule, how many protons are needed Each NADH = Each FADH2 =

- 4 protons. - 0 protons (because it does not traverse the membrane, it can't pump protons). - 4 protons. - 2 protons. - 10 protons pumped because the electrons go through Complex I, III, and IV (So 4 + 4 + 2). - 6 protons pumped because the electrons go through Complex II, III, and IV (so 0 + 4 + 2). - 3 protons are needed. - 3ATP - 2 ATP

Differentiate between ketogenic and glucogenic amino acids. Which amino acids are exclusively ketogenic? Which are both ketogenic and glucogenic? As long as you know these two groups, you don't need to recall the exclusively glucogenic amino acids—they are simply all other amino acids not included on one of these two lists

- A ketogenic amino acid is degraded into acetyl CoA or acetoacetyl CoA (ketone bodies) through ketogenesis. The carbons of ketogenic amino acids are ultimately converted to CO2 in the citric acid cycle (because acetyl CoA carbons are converted to CO2). Leucine and lysine are both ketogenic. Glucogenic amino acids can be converted to glucose through gluconeogenesis. They are converted first to alpha keto acids and then to glucose in the liver. Some amino acids are both ketogenic and glucogenic: isoleucine, phenylalanine, tryptophan, tyrosine, and threonine are both. If you can remember those 5 and the 2 that are ketogenic, all the rest are glucogenic

Consumption of ATP Hydrolysis equation: ATP hydrolysis is almost always coupled to another reaction or process, such that the free energy released can be utilized to?

- ATP + H2O → ADP + Pi + energy. Note that inorganic phosphate (Pi) is created rather than a phosphate group being added to another molecule - drive another reaction or do work (e.g., cocking the myosin head)

Citric Acid Cycle: [a.k.a., Krebs Cycle or Tricarboxylic Acid Cycle (TCA)] The first substrate of the citric acid cycle is ? Acetyl-CoA metabolic origin in most often thought of as a? Acetyl-CoA is also a product of what 2 other processes?

- Acetyl-CoA - pyruvate from glycolysis converted to Acetyl-CoA by the PDH Complex (carbohydrate origin). -Acetyl-CoA is also the primary product of the beta-oxidation of fatty acids (lipid origin), and one of the products of amino acid metabolism (protein origin).

Tissue-Specific Metabolism: Different tissues use different fuel sources preferentially. Liver = in well-fed state? during fasting? Muscle: Differs by muscle type and duration of use. Cardiac = well-fed state? if fasting? Skeletal = well-fed state? if fasting?

- Glucose in well-fed state; Fatty acids during fasting, but NO ketones (lacks enzyme) - Fatty acids during well-fed state; Fatty acids and ketones if fasting - Glucose during well-fed state; Fatty acids and ketones if fasting

β-Oxidation of Fatty Acids: Process: Carbons are removed two at a time to form? which is then fed into? What is required? For example, many students fail to remember that ADP is actually required for glycolysis—easy to do because we think of glycolysis as making ATP, not so much as using ADP (Recall that glycolysis also requires exactly 2 ATP and 2 NAD+ ], in addition to 4 ADP).

- Acetyl-CoA, the Citric Acid Cycle. - The MCAT loves to ask questions about what is required by a biochemical pathway. However, they most often present these question types by asking you to predict what would happen if a given molecule were absent or unavailable.

Consumption of ATP Phosphoryl Group Transfers: Glucose + ATP → ?

- As above, ATP → ADP + energy, but the phosphate is transferred onto another molecule, rather than being releases as Pi - Glucose-6-Phosphate + ADP (occurs during glycolysis)

Non-Template Synthesis: ? The moniker "non-template" is used because?

- Biosynthesis of lipids and polysaccharides (carbohydrates). - the synthesis of fats and carbohydrates does not follow a template as do protein and nucleic acid synthesis

Obesity and Regulation of Body Mass: Body Mass Regulation: ? HORMONES = ? Threshold for weight gain is lower than ? Healthy individuals burn carbohydrates, fats, and proteins in what order

- Combination of hormones, food intake, and activity level - Leptin, Ghrelin, and Orexin - for weight loss - carbohydrates first, then fats, then proteins

Catecholamines: Dopamine is? Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline) are? They also have a "glucagon-like" effect, but should be thought of? Fatty acids are mobilized for? Glycogenolysis ?

- Dopamine, Epinephrine, and Norepinephrine. - CNS neurotransmitter - the two metabolic hormones. - as causing a more rapid "mobilization" of energy stores necessary for the "fight or flight" response. - oxidation - increased.

Citrate-Acetyl-CoA Shuttle: (a.k.a., Tricarboxylate Transport System) PROBLEM: SOLUTION:

- During periods of energy abundance, Acetyl-CoA groups in the mitochondria are redirected from the Citric Acid Cycle to fatty acid synthesis. However, fatty acid synthesis occurs in the cytosol and Acetyl-CoA cannot pass through the inner mitochondrial membrane. - Acetyl-CoA is combined with OAA to form citrate (normal first step of Citric Acid Cycle). Citrate is able to pass through the membrane, and is them converted back to OAA and Acetyl-CoA in the cytosol

ALLOSTERIC ENZYME = ? ALLOSTERIC REGULATION = Allosteric effects almost always result from? Allosteric regulator molecules always binds? In other words, the effect is a change in?

- Enzymes that change conformation and/or affinity for their substrate upon binding of an allosteric regulator molecule. - The general term used to refer to the process of allosteric regulators binding to enzymes to either upregulate or downregulate their activity. - conformational changes. - AWAY FROM THE ACTIVE SITE. - the enzyme itself, NOT inhibition by competing with the substrate for the active site.

Carnitine Shuttle PROBLEM: SOLUTION:

- Fatty acids cannot pass through the inner mitochondrial membrane, where they need to be in order to go through β-oxidation. - The enzyme Carnitine acyltransferase attaches the fatty acyl group from an acyl-CoA to the hydroxyl group of carnitine. A translocase enzyme on the inner mitochondrial membrane moves one acyl-carnitine into the matrix and one carnitine back out

For most bacteria the sole route of metabolizing glucose is? Fermentation is used by animals only during?

- Fermentation (Anaerobic Glycolysis) - oxygen debt (i.e. periods of prolonged exercise), and in erythrocytes

Metabolic States: Well-Fed State (a.k.a., Postprandial, Absorptive) =? insulin levels? glucagon levels? rate of anabolism (vs. catabolism)? rate of glycogen synthesis? rate of fatty acid synthesis ?

- First few hours after eating a meal. - High insulin levels - low glucagon levels - High relative rate of anabolism (vs. catabolism) - High rate of glycogen synthesis - High rate of fatty acid synthesis

Formation of ATP Substrate-Level Phosphorylation = LOCATION: The ATP formed during glycolysis is an example of?

- Formation of ATP from ADP in which the source of the necessary phosphate is a phosphate bound to another molecule (i.e., the "substrate") . To proceed, this process MUST be coupled to an exergonic reaction - Primarily in the cytosol, as part of glycolysis, BUT also in the matrix of the mitochondria where GTP is formed during the Citric Acid Cycle - substrate -level phosphorylation

Formation of ATP Oxidative Phosphorylation = LOCATION: The ATP formed by the ATP Synthase Complex in the mitochondria is an example of?

- Formation of ATP out of ADP and Free Organic Phosphate (Pi) by harnessing the energy of the proton gradient across the inner mitochondrial membrane. This proton gradient is created as a result of coupling the oxidation of highenergy molecules such as NADH and FADH2 to the pumping of protons - Exclusively in the mitochondrial matrix - Oxidative Phosphorylation

ΔG = ΔG° = ΔG°' = For the MCAT, think of ΔG° and ΔG°' as essentially

- Free energy change at some present, non-standard set of conditions - Free energy change at standard conditions: 25°C , 1 atm, and [1M] of all species - Free energy change at standard physiological conditions, pH = 7 - the same thing. They both represent a standard state "from-the-textbook-table" value for Gibbs free energy calculated at a point where we have the exact same concentrations of all species, both products and reactants (i.e., Q = 1). Just remember that the prime (') symbol means it is at physiological pH too

LIVER: Fructokinase converts Fructose → Fructose-1-phosphate aldolase converts Fructose-1P → Triose phosphate isomerase converts DHA-P →

- Fructose-1P - Glyceraldehyde-3P + Dihydroxyacetone-P (DHA-P) - Glyceraldehyde-3P (5th step GLY)

Tissue-Specific Metabolism Brain = well-fed state? fasting? prolonged fast or starvation? Adipose Tissue = well-fed state? fasting? Red Blood Cells = well-fed state? fasting?

- Glucose during well-fed state; Glucose if fasting; Ketones if prolonged fast or starvation - Glucose in well-fed state; Fatty acids during fasting - Glucose in all states; ALWAYS via anaerobic glycolysis

Galactose Metabolism: The entire pathway is a bit too complex for the scope of the MCAT; Focus on the following: In multiple steps (UDP = coenzyme) Galactose is converted → Phosphoglucomutase converts Glucose-1P →

- Glucose-1P - Glucose-6P (2nd step GLY)

Propose an explanation for the fact that erythrocytes use fermentation to convert pyruvate into lactate, even in the presence of oxygen

- Mature erythrocytes lack cellular organelles, they are basically sacks of hemoglobin. This means they also lack mitochondria, the normal location of the citric acid cycle, ETC, and oxidative phosphorylation. Red blood cells use fermentation—even in the presence of oxygen—because they lack the cellular machinery found in other cells and therefore fermentation is their only route to produce energy

β-Oxidation of Fatty Acids: Location:? PROBLEM:? SOLUTION?

- Mitochondrial matrix. Exception = Extra-long-chain fatty acids first enter a peroxisome and are catabolized into smaller pieces. These pieces can then be oxidized in the mitochondria. - Activated fatty acids cannot cross the inner mitochondrial membrane to reach the matrix. - Carnitine Shuttle (Carnitine-acylcarnitine translocase)

Malate-Aspartate Shuttle PROBLEM: SOLUTION:

- NADH cannot pass through the inner mitochondrial membrane. Therefore, NADH produced from glycolysis cannot enter the ETC without the help of this shuttle. - NADH donates two electrons to oxaloacetate (OAA) converting it to malate. Malate passes into the matrix via the MALATE-α-KETOGLUTARATE ANTIPORTER. Inside the matrix, malate is converted back into OAA, regenerating NADH. OAA is then converted into asparate so that it can be pumped back into the cytosol via the GULATAMATE-ASPARTATE SHUTTLE

What is necessary for the production of Glutathione? Glutathione is? R5-P is used to? R5-P is what?

- NADPH - the most important antioxidant in counteracting the damaging impact of the peroxide and radical byproducts of oxidative respiration - synthesize nucleotides - It is the oxygen-bearing ring of all nucleotides, including the famous deoxy-ribo-nucleic acid.

Fatty-Acid Synthesis: LOCATION:? Fatty-Acid synthesis is always the construction of ? This occurs in? Other forms of lipid synthesis, such as synthesis of phospholipids and steroids, occurs on? Source of Acetyl-CoA:?

- Occurs primarily in the cytosol of liver cells. - 16-carbon palmitic acid, the only fatty acid the human body can synthesize from scratch. - in the cytosol. - the smooth ER. - The Citrate Shuttle (Recall that acetyl-CoA groups cannot pass through the inner mitochondrial membrane, so funneling fatty acids from the mitochondria to the cytosol for fatty-acid synthesis REQUIRES this shuttle).

The Electron Transport Chain (ETC): What is the difference between Substrate-Level Phosphorylation and Oxidative Phosphorylation? Which process occurs during the Krebs Cycle?

- Oxidative Phosphorylation - Substrate level phosphorylation is the process by which a phosphate group is transferred to ADP or GDP from a phosphorylated intermediate. The Citric Acid Cycle uses substrate level phosphorylation. Oxidative phosphorylation occurs in ATP synthase in the electron transport chain. This process combines ADP and inorganic phosphate to generate ATP through the generation of a proton gradient by transporting electrons

The Pentose Phosphate Pathway (PPP) When you see PPP THINK: NADPH is NADPH → NADPH is used during?

- PPP = 1) NADPH synthesis and 2) Ribose-5-Phosphate (R5-P) - an important reducing agent - NADP+ - "Reductive Biosynthesis"—a general term referring to a large number of reactions used to synthesize fatty acids and sterols

PDH Complex: Think of the PDH complex as the linkage between what to processes? Pyruvate = 3 Destinations:

- Pyruvate → Acetyl-CoA - glycolysis and the Citric Acid Cycle. It is a set of three enzymes that convert pyruvate to acetyl-CoA, which is the first substrate of the Citric Acid Cycle - 1) PDH Complex → Acetyl-CoA (Feeds into the Citric Acid Cycle) 2) Lactate Dehydrogenase → Lactate (Fermentation) 3) Pyruvate Carboxylase → Oxaloacetate (1st step of gluconeogenesis

When you see: NADH/NAD+, NADPH/NADP+ FADH2/FAD, FMNH2/FMN, semiquinone (an FMNH° radical), ubiquinone, or cytochrome, THINK: These are soluble electron carriers and as they pass from one form to the other there is ALWAYS?

- REDOX! - electron transfer and therefore oxidation-reduction

The Pentose Phosphate Pathway (PPP) NON-OXIDATIVE PHASE: SUGAR POOL = R5-P is funneled into? KNOW THIS: 2 things

- Ribulose-5-Phosphate ↔ R5-P ↔ SUGAR POOL ↔ Glucose-6-Phosphate - Erythrose-4-P, Sedoheptulose-4-P, Xylulose-5-P, and a number of other carbohydrates you do NOT need to know by name for MCAT-2015 - nucleotide synthesis. (Note that R5P and Ribulose-5-Phosphate are two different molecules) - 1) Conversion into the SUGAR POOL from Ribulose-5-Phosphate, interconversions between sugars within the pool, and conversion to Glucose-6-P are all catalyzed by either Transketolase or Transaldolase. 2) All of the reactions into, out of, and inside of the pool are reversible

Glycerol-3-Phosphate Shuttle PROBLEM: SOLUTION:

- Same as Malate-Aspartate Shuttle, NADH cannot enter the mitochondria to participate in the ETC . - Think of this as a second solution to the same problem, but a minor contributor. The MalateAspartate Shuttle is the major contributor and the Glycerol-Phosphate Shuttle helps out. - NADH donates two electrons to dihydroxyacetone phosphate (DHAP) to form Glycerol-3-Phosphate (G3P). G3P is converted back into DHAP by Mitochondrial G3P dehydrogenase, an enzyme bound to the cytosolic surface of the inner mitochondrial membrane. The enzyme passes the electrons to FAD to form FADH2

Biological Oxidation-Reduction Reactions Biological REDOX reactions follow all of the same basic science principles as the REDOX reactions you studied in the General Chemistry chapters Half-Reactions: GADP + NAD+ + Pi →

- Separation of a complete reaction into its oxidation and reduction half-reactions. For example, consider Step 6 of glycolysis - 1,3-BPG + NADH

Chemiosmotic Coupling = ? Uncoupling: It may be said that Drug X "uncouples" ? This means the gradient is no longer? For example, this could be because a drug inserted proton channels into the inner mitochondrial membrane. The ETC would continue to pump protons, but because protons have an alternate route back into the matrix, the two processes would ?

- The direct coupling of the energy inherent in the electrochemical gradient across the inner mitochondrial membrane to the phosphorylation of ADP (to form ATP). - the ETC or the electrochemical gradient from oxidative phosphorylation. - directly driving ATP production at the ATP synthase. - no longer be directly or fully "coupled."

Proton Motive Force = ? The energy released as protons move down their concentration gradient AND down their electrical gradient, toward the mitochondrial matrix is used ?

- The driving force of the electrochemical gradient established by the electron transport chain that is harvested by ATP synthase to produce ATP. - by ATP synthase to add a free organic phosphate to ADP, creating ATP.

What structural aspects of ATP account for its ability to serve as an effective energy storage molecule?

- The phosphoanhydride bonds that connect the phosphate groups are what make ATP an effective energy store for the cell. This type of bond is highly energetic. At physiological pH, the phosphate groups lose their protons and become negatively charged. The negative charges repel one another, and with three charged phosphate groups, there is a much greater repulsion occurring. Also, ADP and Pi are much more stable than ATP, due to less repulsion and resonance stabilization, so the ΔG of converting ATP to ADP and Pi is very negative

Energetic Steps:

- The precise number of high-energy molecules required, and the NET number of each high-energy molecule produced, per glucose (NADH/NAD +, FAD/FADH2, ADP/ATP or GDP/GTP). The precise location/step within the cycle where these high-energy molecules are required or produced

ATP = ΔG°' for ATP hydrolysis << ? Sequential loss of one phosphate group changes ATP → ? → ? Cyclization takes AMP → ? You'll want to be familiar with cAMP because ?

- The primary energy currency of the human body - 0 (ΔG°' = -30.5 kJ/mol) - ADP → AMP - cAMP - it is the most common second messenger molecule encountered on the MCAT

Carbohydrate Metabolism definition: Respiration:

- The sum of all chemical reactions in the body - Although this is often associated with breathing, its definition in this context is the breakdown of macromolecules into smaller species to harvest energy in the form of ATP."

Bioenergetics are? As a review from the General Chemistry 1 chapter, describe the "Fundamental Thermodynamic Relation" that correlates enthalpy, entropy and Gibbs free energy. Draw a fourquadrant chart showing all possible combinations for the signs of ΔS and ΔH for a reaction. For each scenario predict the sign of ΔG and whether or not the reaction will be spontaneous

- The thermodynamics of biological systems; analogous to biochemistry being the chemistry of biological systems - First, keep in mind the first two laws of thermodynamics. One, the total energy of a system and its surroundings is constant. Two, the total entropy of a system plus its surroundings is always increasing. The fundamental thermodynamic relation can be described with the equation ∆G= ∆H-T∆S , where G is Gibbs free energy, H is enthalpy, S is entropy, and T is temperature (in kelvins). A reaction will be spontaneous if ΔG is less than 0, non-spontaneous if ΔG is greater than 0, and at equilibrium if ΔG is = 0. A reaction is favorable if ΔH is negative and/or ΔS is positive. When ΔH is negative and ΔS is positive, the reaction will be spontaneous. When ΔH is positive and ΔS is negative, the reaction will not be spontaneous. In any other situation, the result will depend on the values of H and S

Starvation glucagon and epinephrine levels? rate of gluconeogenesis? rate of fatty acid oxidation, resulting in?

- VERY HIGH glucagon and epinephrine levels - VERY HIGH rate of gluconeogenesis - High rate of fatty acid oxidation, resulting in ketone bodies and acidosis

Explain why the oxidation of FADH2 produces fewer ATP than the oxidation of NADH

- When NADH is oxidized, the electrons flow through Complexes I, III, and IV. When FADH2 is oxidized, the electrons flow through Complexes II, III, and IV. Because Complex I pumps 4 electrons and Complex II pumps 0 electrons, oxidation of FADH2 results in fewer protons being pumped. ATP synthase requires the proton gradient to function, and so fewer protons pumped will result in fewer ATPs being generated

Fructose Metabolism: MUSCLE & KIDNEYS: Hexokinase converts Fructose →

- [Primary sugar in many fruits; also a product of sucrose hydrolysis] - Fructose-6P (3rd step GLY)

Feeder Pathways for Glycolysis (GLY): These other pathways funnel into glycolysis Glycogen Metabolism: 1) Glycogen phosphorylase removes glucose residues from the reducing ends of glycogen polymers → 2) Posphoglucomutase converts Glucose-1P →

- [glycogen = glucose polymer, mostly in liver, also high in muscle] - Glucose-1P - Glucose-6P (2nd step GLY)

Noteworthy Differences between "Lab Thermodynamics" and Bioenergetics in Living Systems Living systems must maintain? Many aspects of a living system require a large, negative ΔS due to? ΔG for many anabolic and metabolic biochemistry reactions is?

- a NON-equilibrium state! - all macromolecules and systems being highly ordered compared to their precursors - positive

Differences in the Oxidation Process for UNSATURATED Fatty Acids: Normal β-oxidation includes the creation of what bond in what position (between carbons 2 and 3, counting from the carbonyl carbon)? As successive rounds of oxidation occur, if a doublebond ends up in this position things may proceed as normal. If a double bond is in another position (e.g., 3-4) can β-oxidation proceed? The enzyme Enoyl-CoA isomerase catalyzes? In some cases, the process results in a conjugated double bond, which will? In that case, a pair of enzymes does what?

- a double bond in the 2-3 position - no - the movement of double bonds to the 2-3 position. Oxidation can again proceed. - also stop β-oxidation -deletes one of the two double bonds and then the same Enoyl-CoA isomerase moves the remaining double bond to the 2-3 position.

Equilibrium is NOT the same as a steady state! Equilibrium is? If you were at complete equilibrium with your environment, you would be dead! Living systems must constantly invest energy to maintain a steady homeostatic state that is?

- a dynamic state existing at the lowest possible entropy and energy for that system - FAR away from equilibrium

HUMAN BODY:Open or Closed System. As a whole, and more specifically, at environmental interfaces (e.g., skin and air, lung alveoli and air, etc.) biological systems are? Why? However, at the cellular and molecular level the system is considered, or assumed to be?

- open - because they can exchange both mass and energy with the environment - a CLOSED system. It can exchange energy but not mass with the surroundings

A ketogenic amino acid is degraded into? through? The carbons of ketogenic amino acids are ultimately converted to? What two amino acids are both ketogenic? Glucogenic amino acids can be converted to glucose through? They are converted first to? and then to? Some amino acids are both, which ones are both?

- acetyl CoA or acetoacetyl CoA (ketone bodies) through ketogenesis. - CO2 in the citric acid cycle (because acetyl CoA carbons are converted to CO2). - Leucine and lysine - gluconeogenesis. - alpha keto acids and then to glucose in the liver. - isoleucine, phenylalanine, tryptophan, tyrosine, and threonine are both. If you can remember those 5 and the 2 that are ketogenic, all the rest are glucogenic

Allosteric Control: FIRST: Metabolic regulation often involves a downstream product inhibiting? That makes perfect sense because the first few product molecules synthesized are very unlikely to immediately interact with the enzyme—meaning? However, as that product builds up, the upstream enzyme will begin to interact with that product frequently, and the enzyme will be? In this way production is slowed only after?

- an upstream enzyme. - it won't be shut off too early. - inhibited. - the necessary amount of a biomolecule has been produced.

T3 & T4: These thyroid hormones increase? Both are secreted by? in response to?

- basal metabolic rate - thyroid - TSH from the anterior pituitary

Gluconeogenesis is needed when? As such, the enzymes are regulated oppositely to those in glycolysis such that when one pathway is activated? Fructose 1,6-bisphosphatase is inhibited by? and stimulated by? Both pyruvate carboxylase and phosphoenolpyruvate are inhibited by? These enzymes are the counterpart to?

- energy levels are high and glucose levels are low, the opposite of when glycolysis is needed. - the other is being actively inhibited, and vice versa. - AMP, ATP, exactly opposite of its glycolysis counterpart, phosphofructokinase. - ADP. - pyruvate kinase in glycolysis.

The ATP → ADP → AMP transitions all have a negative ΔG°' and are therefore? The AMP → cAMP transition is? cAMP is higher or lower in energy than ATP?

- exergonic - endergonic - higher

Anaerobic respiration will typically refer to? Humans use aerobic respiration to generate ? However, we use anaerobic respiration in our muscles during exercise that results in a buildup of? Many bacteria and yeast use anaerobic respiration, including during?

- fermentation, using glycolysis in the absence of oxygen, or the lactic acid cycle in muscles. - the vast majority of our ATP. - lactic acid. - fermentation.

Glycogenesis, the synethesis of glygogen, is regulated oppositely to? When glucagon and epinephrine are present in the bloodstream, the cAMP cascade is? Protein kinase A phosphorylates glycogen synthase, but this phosphorylation does what to the enzyme (instead of activating, as it does with glycogen phosphorylase). When the cAMP cascade is withdrawn, what will dephosphorylate glycogen synthase, stimulating glycogen synthesis. This way, the same stimulus will simultaneously?

- glycogenolysis. - stimulated, as discussed in part C. - inhibits - protein phosphorylase I - shut down one pathway and turn on the other

The electron transport chain is stimulated by? Additionally, there are many poisons that inhibit ETC. Rotenone, an insecticide, blocks electron transfer in? Cyanide, azide, and carbon monoxide block? Oligomycin, an antifungal agent, prevents?

- high levels of ADP and inhibited by high levels of ATP. - electron transfer in NADH-Q oxidoreductase. - electron flow in cytochrome c oxidase. - proton flow through ATP synthase.

Shuttles are used to transport molecules across? In some cases, the molecule is simply activated by adding a functional group that ? In other cases, only a portion of the membrane-impermeable parent molecule, such ? Sometimes, only electrons are passed through the membrane and the entire parent molecule remains? Some shuttles do not require energy input while others do. When energy is required, it?

- impermeable membranes. - increases its solubility. - as functional group, is passed through the membrane. - outside. - decreases the net energy value for oxidation of the shuttled molecule. For example, NADH from glycolysis produces one less ATP than an NADH formed in the mitochondrial matrix.

The four enzymes specific to gluconeogenesis replace three glycolytic enzymes which all catalyze _________ reactions. Those three steps that are replaced are all what type of reactions?

- irreversible reactions. - phosphorylation reactions

Ketogenesis is the process by which? When does this occur? Ketogenesis is able to provide energy by? This occurs in the liver. Ketolysis is the utilization of ketone bodies by converting them to? This occurs in organs other than the liver mainly? When blood glucose is low, β-oxidation and ketogenesis occur in? Ketone bodies are transported out of the liver to key tissues, where they can be used for energy through? The brain (and CNS) in particular relies on ketone bodies when?Most other tissues and organs can use fatty acids for energy when glucose is low, but the CNS relies on?

- ketone bodies are produced through the breakdown of fatty acids. - during periods of starvation when blood glucose levels drop and no further source of carbohydrate fuel is available. - generating acetyl CoA to be fed into the citric acid cycle. This occurs in the liver. - acetyl CoA for energy. - heart and brain). - the liver. - ketolysis. - glucose is not abundant. - glucose primarily, and ketone bodies during periods of starvation, for fuel.

Fasting State (a.k.a., Postabsorptive) insulin levels? glucagon levels? rate of catabolism (vs. anabolism; reversal of the well-fed state)? Glycogenolysis =? Gluconeogenesis = ?

- low insulin levels -High glucagon levels -Higher relative rate of catabolism (vs. anabolism; reversal of the well-fed state) - Immediate increase - Delayed increase (~12 hrs.)

From a single number and sign we know a lot about a reaction, including whether products or reactants are? Suggest two reasons biochemists do not use ΔG° directly to describe biochemical reactions in the human body?

- more favored, whether it will give off or require free energy, and whether products or reactants will predominate at equilibrium - ΔG°, or standard free energy, is the ΔG of a reaction at "standard" conditions, when each reactant is at a concentration of 1.0 M. In the body, this is almost never the case. Further, reactions in the body are typically at near-equilibrium, when ΔG is very close to 0. ΔG° of a single reaction in the body is typically not very useful, as reactions are often coupled or regulated in some way such that something may appear to be non-spontaneous, but in the body it occurs spontaneously

Protein Kinases are the enzymes that catalyze? (Important Note: Dephosphorylation can also turn a molecule on or off, but it does not usually result in the re-formation of ATP. Phosphorylation and dephosphorylation are opposite regulatory functions, but they are NOT a reversal of the same reaction. Phosphorylation uses protein kinases and ATP, dephosphorylation uses phosphatases and produces free Pi.) Glycogen Phosphorylase-A (GPA) is the enzyme that? ** = active ; # = inactive GPA# + 2ATP →

- phosphorylation coupled to ATP cleavage - catalyzes the breakdown of glycogen to glucose - GPA-PP** + 2ADP

Protein Metabolism: Most amino acids can be broken down into either? and fed into the? The remaining amino acids can be transformed into? Notice that we have now seen that the pyruvate/acetyl-CoA fed into the Krebs cycle can be derived from?

- pyruvate or acetyl-CoA and fed into the Citric Acid Cycle. - various other Citric Acid Cycle intermediates (often alpha-ketoglutarate, Step and enter into the cycle at the appropriate point. - carbohydrates, fats, or proteins.

Anabolism of Fats & Carbohydrates: Anabolism is the opposite of catabolism and is more often referred to as ? Anabolic processes construct larger macromolecules out of? catabolic processes breakdown macromolecules into?

- synthesis. - smaller precursors - smaller precursors or monomeric units.

"Dynamic Steady State" describes? Example, your body temperature remains a fairly constant 98.6F, and yet?

- the ability of living things to maintain a constant, steady internal environment that is NOT IN EQUILIBRIUM WITH ITS SURROUNDINGS - the room you are in right now is probably about 75F. Further, the environment around you is in constant decay—moving organized, complex, high-energy states toward disorganized, simpler, low-energy states

ETHANOL FERMENTATION: (primarily yeast, a few bacteria) Ethanol is produced and is the final electron acceptor. Ethanol fermentation is unique compared to lactic acid fermentation in that? LACTIC ACID FERMENTATION: In lactic acid fermentation, lactate is produced and is? Fermentation is IMPORTANT because? NAD+ regeneration is necessary for?

- the carbon skeleton changes. Pyruvate (3C ) is broken down into ethanol (2C ) and CO2 - the final electron acceptor - it regenerates NAD+ so that glycolysis can continue - both human fermentation during oxygen debt and yeast/bacterial fermentation

Protein Metabolism: Transamination: A key step in protein metabolism for energy is transamination of amino acids—which is?

- the exchange of an amine group on one molecule for a carbonyl group on another . For example, transamination of Glu forms alpha-ketoglutarate, an intermediate in the Citric Acid Cycle.

Think of ΔG°' as? Think of ΔG as? ΔG°' is fixed and predetermined for a given reaction at a given temperature. It ONLY represents the reaction under all of those strictly standardized criteria. By contrast, ΔG can be measured? Pause the reaction at any precise moment of your choosing, subtract the sum of the free energy of the reactants present at that moment from the sum of the free energy of the products present at that moment, and the resulting value will be?

- the fixed, unchangeable value - the variable one - anywhere, at any time during a reaction - ΔG

The pentose phosphate pathway is primarily controlled by? The first enzyme, glucose 6-phosphate dehydrogenase, is inhibited by NADP+ because?

- the levels of NADP+. - because NADP+ is needed as the electron acceptor for the reaction

Ketone Bodies: Acetone (no energy value), Acetoacetate (energy), and 3-Hydroxybutyrate (energy) Formed by? Two of the three can be used for energy during ? Ketone bodies CANNOT be used by the liver during fasting because? Too much fatty acid metabloism can cause? Diabetes can also cause ketoacidosis because ?

- the liver during prolonged fasting periods as byproducts of increased fatty acid metabolism. - fasting periods by the heart and brain. - lacks a necessary enzyme. - ketoacidosis, or excess acidity of the blood. - a lack of insulin available for sugar uptake from the blood forces the liver to switch to fatty acid metabolism almost as if the person were fasting.

POTENTIALLY CONFUSING LOCATION ISSUES: Lipids are metabolized for energy in ? Synthesized in? Modified at the? Fatty acid synthesis in the cytosol stops at the? Elongation and modification (e.g., desaturation) occur at?

- the mitochondria - the cytosol (mostly hepatocytes) - the smooth ER (SER) - the 16-carbon palmitic acid (technically, it ends by forming palmitoyl-CoA). - the Smooth ER.

Much as glycolysis and gluconeogenesis are reciprocally regulated, glycogenolysis and glycogen synthesis are regulated in opposite ways. Glycogenolysis, the breakdown of glycogen into glucose 6-phosphate, is stimulated by ? In both cases, the hormones stimulate a cAMP cascade, which ultimately activates? This phosphorylates phophorylase kinase, which? Glycogenolysis is shut down when? Without the stimulating hormones, the cAMP cascade is?

- the presence of glucagon and epinephrine in the bloodstream. - protein kinase A. - activates glycogen phosphorylase. - the stimulating hormones are gone from the blood stream. - withdrawn, and protein phosphatase I dephosphorylates glycogen phosphorylase.

Gluconeogenesis: Conceptualized as? Three glycolytic enzymes are substituted for? When you see gluconeogenesis, THINK:

- the reversal of glycolysis to produce glucose from pyruvate - four unique enzymes specific to gluconeogenesis - Gluconeogenesis = LIVER, fasting, and the need to increase blood sugar

The "5" in R5P refers to? Glucose-6-P → 6-Phosphogluconate → Ribulose-5-P, The two steps outlined are both coupled to the conversion of?

- the same 5' carbon we discussed frequently in the Biology 2 chapter in terms of the 3' and 5' ends of a nucleotide polymer strand - NADP + to NADPH

Respiration is a process in which an in organic compound serves as? Aerobic respiration uses oxygen as ? Anaerobic respiration uses ? For question purposes, aerobic respiration involves all the reactions involved?

- the ultimate electron acceptor in order to generate ATP. - the final electron acceptor - a molecule other than oxygen. - in the citric acid cycle and electron transport.

Glucocorticoids also act on the hippocampus, amygdala and frontal lobes to? Multiple studies have demonstrated that high levels of glucocorticoids have increased recall of? Glucocorticoids also enhance? The level of cortisol in the blood, graphed against memory performance, follows the what shape predicted by the Yerkes—Dodson Law?

- to enhance emotional memory. - "flashbulb memories"—those associated with highly emotional events, either positive or negative. -attention and arousal. - the inverted U-shape

Exercise Duration Dependent: Creatine phosphate is a very-short-lived energy source for? the main fuel is? switching from oxidative use of glucose to lactic acid fermentation during? if exercise continues even longer (i.e., endurance athelete) the muscles must use?

- very-short-lived energy source for short bursts of action; - glucose from the glycogen stores - prolonged exercise - only fatty acids.

It is important to remember that a reaction is almost never going to be in these conditions. Have you ever started a reaction in the lab by mixing together one mole of reactant A, one mole of reactant B, one mole of product C and one mole of product D (even if A and B react in a 2:1 stoichiometry)? Of course not. We generally start reactions with only reactants and the entire purpose is to create our desired product. The primary value of these standard state Gibbs energy values is to know instantly from a number? If ΔG is negative, we know it will proceed from standard state to? If ΔG is positive, we know it will proceed from standard state to?

- which way a reaction will proceed from that hypothetical standard state - the right, and produce more product - the left, and produce more reactants

Equation for ΔG = R is? T is? Q is?

- ΔG°' + RTlnQ - the Universal Gas Law constant - temperature - the reaction quotient

Exergonic = ∆G is negative =

- ∆G is negative - spontaneous

Explain as precisely as possible why the following equality is invalid: ΔG = -RTlnKeq Endergonic = ∆G is positive =

- ∆G°^'= -RTln〖K'〗_eq. ΔG ≠ ΔG°', as explained in part B of Italicized Question #4. The one exception is when Keq = exactly 1.0, as explained in part A of Italicized Question #7 - ∆G is positive - nonspontaneous

1) In glycolysis, how many reactions are regulated? 2) Keep in mind that glycolysis is needed when energy in the cell is low, so regulation will be such that enzymes are activated by? 3) Phosphofructokinase is inhibited by? 4) AMP does what to inhibition of ATP? 5) Glycolysis is stimulated when? 6) and it is reduced when? 7) Hexokinase is another way to regulate? 8) It is inhibited by? 9) Because glucose and glycogen are both converted to glucose 6-phosphate, when this molecule is at high concentration, hexokinase is inhibited because? Glucose will stay at higher concentrations in the blood or be converted to glycogen for storage. 10) The third regulated enzyme is? 11) ATP inhibits pyruvate kinase to do what? 12) Alanine also inhibits pyruvate kinase because?

1) three reactions are regulated. 2) a lack of energy and inhibited when energy is abundant. 3) high levels of ATP and is the main source of regulation for glycolysis. 4) AMP reverses the inhibition of ATP, and so the ratio of ATP to AMP is crucial to determining the activity of glycolysis. 5) energy available to the cell falls 6) when energy increases. 7) glycolysis. 8) glucose 6-phosphate, its product. 9) the cell has plenty of access to energy. Glucose will stay at higher concentrations in the blood or be converted to glycogen for storage. 10) pyruvate kinase. 11) to slow glycolysis. 12) pyruvate is used as a building block for amino acids, and a high concentration of alanine signals that building blocks aren't needed

T/F? a) If Keq = 1, ΔG° = 0, b) If Keq = 1, ∆G = 0, c) If Keq = Q, ∆G = 0, d) If Keq = Q, ΔG° = 0 e) If Q = 1, ∆G = 0, f) If Keq = 1, ∆G = ΔG°, g) If Q = 1, ∆G = ΔG°, h) If Keq > 1, ΔG° must be negative, i) If Keq > 1, ∆G must be negative

7. A) True. If Keq = 1 then ΔG° = 0, since ΔG° = -RTlnKeq, and the ln(1) = 0. However, do not confuse this with the fact that ΔG = 0 at equilibrium in every case. For all other cases, ΔG° does NOT equal zero at equilibrium (but ΔG does). ΔG° = 0 at equilibrium ONLY if Keq for that reaction = exactly 1.0. In this rare case, ΔG = ΔG°. This is proven by the equation: ΔG = ΔG°' + RTlnKeq. If Keq = 1, then the second term is zero and ΔG = ΔG°. B) False. ΔG = ΔG° + RTln(Q), so ΔG = -RTln(Keq) + RTln(Q), and if Keq = 1 then ΔG° = 0 and ΔG = RTln(Q), which is not 0. C) True. If Keq = Q, the reaction is at equilibrium, and ΔG = 0. D) False. The reaction is at equilibrium, but ΔG° is not 0 at equilibrium, as discussed in Italicized Question #4. E) False. ΔG = ΔG° + RTln(Q), and if Q is equal to 1 then ΔG = ΔG° because ln(1)=0 F) False. ΔG = ΔG° + RTln(Q), so ΔG = -RTln(Keq) + RTln(Q), and if Keq = 1 then ΔG° = 0 and ΔG = RTln(Q), which are not equal. G) True. ΔG = ΔG° + RTln(Q). Since Q = 1 and Ln(1) = 0, ΔG = ΔG°. H) True. ΔG° = -RTlnKeq I) False. ΔG = ΔG° + RTln(Q), and various concentrations of reactants and products (Q) can affect ΔG, regardless of what the Keq and ΔG° values are

The translocation of a proton through the F0 moiety of ATP synthase is associated with a very large negative ΔG. Suppose a localized change in temperature decreased the free energy released by this reaction. What would be the likely effects on: a) ATP production, b) ETC function, c) the strength of the electrochemical gradient, and d) the Citric Acid Cycle. (Note: Assume other metabolic processes and enzymes do not experience the same temperature change.)

A decrease in the free energy released by a reaction will, in general, decrease the rate of the reaction. In this case, decreasing the free energy released as a result of translocating a proton through ATP synthase will A) decrease ATP production, because the equilibrium will be shifted such that the phosphorylation of ADP to ATP will happen at a slower rate. B) Electron transport chain function will decrease as well because there won't be as many protons to pump out by Complexes I, III, and IV if they aren't being pumped in at the same rate by ATP synthase. ETC function will not decrease as much or as quickly as ATP production because the enzymes involved are not directly affected by the free energy decrease. C) The electrochemical gradient will increase slightly because protons will be pumped out by Complexes I, III, and IV, but ATP synthase won't be pumping them back in as quickly. D) The citric acid cycle will still function normally because it does not depend on ATP synthase.

Students frequently hold misconceptions about ΔG and ΔG°'. Check yourself with the following: T/F? a) For Reaction X, ΔG = -30.78 kJ. For Reaction Y, ΔG = 22.5 kJ. It can be concluded that Reaction Y is closer to its equilibrium than is Reaction X, b) At equilibrium, ΔG°' = 0, c) At equilibrium ΔG = 0 d) For a given reaction at a given temperature, there are an infinite number of different ΔG°' values associated with different ratios of products to reactants, e) For a given reaction at a given temperature, there are an infinite number of different ΔG values associated with different ratios of products to reactants, f) ΔG°' represents the free energy change for a complete conversion of all reactants to products

A) T. Reaction X, ΔG = -30.78 kJ. Reaction Y, ΔG = 22.5. Reaction Y is closer to equilibrium. The sign of ΔG tells us the direction in which the reaction needs to proceed to reach equilibrium and the magnitude tells us the relative distance from equilibrium. If the magnitude is zero, ΔG° = 0, then we know the reaction is a equilibrium. B) F. ΔG°' = 0 does not represent equilibrium. At equilibrium, ∆G°^'= -RT lnKeq because ∆G= ΔG°^'+RT lnKeq and at equilibrium, ΔG = 0 C) T. ΔG = 0 at equilibrium D) F. ΔG°' is independent of the concentrations of reactants and products. It is a set standardized value taken from a table for the given reaction under standard conditions, which include 1M concentrations of each species. The ΔG°' value is SPECIFIC to 1M concentrations of products and reactants (and other standard states such as temperature and pressure). If a reaction with a certain ΔG°' value is NOT at standard conditions (say the ratios of products and reactants are quite different from 1M each) then the reaction has some ΔG value (Note: NOT ΔG°') associated with those particular non-standard conditions. However, the ΔG°' for that reaction would still be whatever is listed in the table. Some texts refer to ΔG as ΔGactual to emphasize that it is Gibbs Free Energy for a reaction at any actual set of conditions other than standard conditions. E) T. ΔG is not associated with standard conditions. ΔG can be calculated for a reaction at any point in time for any concentration of products and/or reactants. F) F. We have noticed a considerable number of students who have this misconception and found it repeated on a professor's website which shows up in a Google search. The value ΔG°' is NOT the free energy change for the completion of a reaction to its endpoint. Recall that almost no reaction ever converts all reactants to products because equilibrium is reached beforehand. Rather, the value ΔG°' represents the free energy associated with proceeding from a standard state concentration (1M of each reactant) to equilibrium. For example, a negative value for ΔG°' indicates that the reactants have more free energy than the products. Thus, running the reaction toward the products results in a lower energy state and is favored. However, as the reaction approaches equilibrium this driving force gradually disappears. At equilibrium, there is no driving force to move in either direction, and thus ΔG = 0 (Note: NOT ΔG°')

ATP Synthase Think: Where does oxidative phosphorylation occurs? The Citric Acid Cycle is NOT oxidative phosphorylation, NEITHER is the ETC . Those are preparatory steps to create the? Most precisely, oxidative phosphorylation is the phosphorylation of?

ATP Synthase: - Oxidative Phosphorylation! - ATP Synthase - electrochemical gradient across the inner mitochondrial membrane so that oxidative phosphorylation can occur. - ADP, using energy from the gradient, and oxygen as the final electron acceptor.

Aldolase catalyzes the breakdown of Fructose 1,6-bisphosphate (F1,6BP) into one molecule of glyceraldehyde-3-phosphate and one molecule of dihydroxyacetone-phosphate (DHAP). If the 2' carbon of F1,6BP is radioactively labeled, aldolase is allowed to turnover a large number of molecules, and isomerase activity is blocked, how will the radio label be distributed? a) equally between F1,6BP and DHAP molecules, b) only on F1,6BP molecules, c) only on DHAP molecules. Explain your answer in detail.

All the radiolabeled molecules will be dihydroxyacetone phosphate. This is because when fructose 1,6-bisphosphate is cleaved, it is cleaved the same way every time. Carbons 1, 2, and 3 become dihydroxyacetone phosphate, and carbons 4, 5, and 6 become glyceraldehyde 3-phosphate. If carbon 2 is labeled, the labeled molecule will always be DHAP. If the isomerase is active, some of the DHAP will be converted to GAP, so the label will be distributed between the two. But without the isomerase, all labeled molecules will be DHAP

Allosteric Control: SECOND: The eventual target molecule, or logical goal of the process, is? For example, ATP acts as? That makes perfect logical sense! When ATP levels are high the process will be? Meanwhile, AMP and ADP are allosteric activators of?

Allosteric Control: - often a major inhibitor that down regulates upstream production. - an allosteric inhibitor of Phosphofructokinase-1 (PFK-1), the enzyme for the rate-limiting step of glycolysis. - downregulated. - PFK-1.

Allosteric Control: THIRD: The most likely step to be regulated in a metabolic pathway is? If the pathway has multiple alternative pathways, it is usually? For example, the first non-reversible step in glycolysis is hexokinase. However, Glucose-6-P has possible alternative fates other than completing glycolysis (e.g., glycogen synthesis, PPP). The next irreversible step is? After this step, all molecules will complete glycolysis and it is indeed the main regulatory point for glycolysis.

Allosteric Control: - the "first committed" step—or the first non-reversible reaction step. - the first irreversible step after which the molecule is COMMITED to finishing the pathway. - is catalyzed by PFK-1.

The post-translational folding of the enzyme ribonuclease-A is associated with a large, negative ΔS for the unfolded-to-folded transition. Ribonuclease-A folds spontaneously because the: A) sum of the heats of formation of all folding interactions in the native conformation is large and negative. B) sum of the heats of formation of all folding interactions in the unfolded conformation is large and negative. C) change in entropy for the unfolded-to-folded transition is large and positive. D) change in entropy for the unfolded-to-folded transition is small and positive

Answer B is false. The total ΔH formation for all folding interactions cannot be large and negative (i.e., highly favored) in the UNFOLDED conformation. If this were true, proteins would not fold spontaneously. Answers C and D are both false because the stem overtly states that the change in entropy is negative. Answer A is correct. The large negative enthalpy that results from folding overcomes the large negative entropy associated with drastically increased order, resultin g in a net negative ΔG according to: ΔG = ΔH - TΔS

Hormonal Control Metabolism Hormones = 5 of them. Glucocorticoids: Cortisol is the most significant example. Recall that cortisol is produced by the adrenal cortex in response to? Glucocorticoids have a "glucagon-Like" effect on metabolism (e.g., stimulating? Glucocorticoids also reduce?

Hormonal Control: - Insulin, Glucagon, glucocorticoids, catecholamines, T3 & T4 (Regulation of blood glucose by Insulin & Glucagon is discussed in the Biology 3 chapter). - ACTH from the anterior pituitary. - gluconeogenesis, glycogenolysis, and fatty acid oxidation). - inflammation

Which metabolic substrates, enzymes, or products are "trapped" in a single cellular compartment? For example, are some found only in the cytosol? Are others trapped in the mitochondrial matrix and cannot leave?

In general, most metabolic substrates are able to move freely or be transported around the cell. This makes sense if you think about how many pathways are linked, which wouldn't be possible if substrates were primarily held in one organelle or another. Enzymes, however, are often "trapped" in one location. Consider the enzymes of the electron transport chain. All of them are membrane proteins, which means that they are always embedded in the inner mitochondrial membrane. Also trapped within the mitochondrial membrane are the cofactors of the ETC, such as ubiquinone and cytochrome c. Glycolysis occurs in the cytoplasm, and as such, the enzymes for glycolysis are located in the cytoplasm. The citric acid cycle occurs in the matrix of the mitochondria, where the enzymes are "trapped." The products of glycolysis and the citric acid cycle can be transported across the membrane and are not trapped

Which molecules are reduced and which molecules are oxidized? Identify the oxidizing agents and reducing agents. Write the reaction as two half-reactions and prove via Hess's Law that they account for this reaction

In the reaction, GADP is the reduced form, NAD+ is the oxidized form 1,3 BPG is the oxidized form, and NADH is the reduced form. Thus NAD+ is being reduced (it is an oxidizing agent) and GAPD is being oxidized (it is a reducing agent). NAD+ + H+ + 2e- → NADH GADP + Pi → 1,3-BPG + 2e- + H+ Together, those equal NAD+ + Pi + GADP → NADH + 1,3-BPG

Three students are reviewing a chart in their biochemistry text showing that many of the individual steps of glycolysis have a positive ΔG' value. Discuss the accuracy and merits of their competing explanations for why glycolysis still occurs readily in living systems: Student A) Enzymes are the solution! Enzymes drastically lower the free energy change to be more negative. Student B) Food energy is the solution! Many biochemical reactions are unfavorable and that is why we must eat—to provide external energy to drive these reactions and maintain disequilibrium. Student C) Reaction coupling is the solution! While some reactions are unfavorable, they are coupled to reactions that are favorable

Several steps in glycolysis have positive ΔG's, but the pathway still occurs spontaneously in cells. The first student hypothesizes that this is due to enzymes lowering the free energy of the equation. However, the ΔG listed for the steps of glycolysis take the enzymes into account, and so the enzymes themselves cannot account for the spontaneity of the overall pathway. Student B thinks that food energy is the solution, and that eating will give the energy needed to drive glycolysis. However, glycolysis is the process through which the body breaks down glucose, which is how the body gains energy from starchy food, so eating more wouldn't drive the reaction forward. It would instead put more glucose into the system, requiring even more glycolysis action. Student C is correct, reaction coupling will drive the entire pathway forward. Some steps in glycolysis have positive ΔG's, but other steps have very negative ΔG's. Those steps require the products of previous steps. Because the reactions are linked by the product of one reaction providing the substrates of the following reactions, the very negative ΔG's will pull the pathway forward, even though the positive ΔG's are earlier in the pathway than the very negative ΔG's

Steps (e) and (f) in Figure 1 represent which kind of reaction, respectively? A) dehydration and reduction B) dehydration and oxidation C) oxidation and reduction D) reduction and oxidation

Step (e) is a dehydration, as indicated by the loss of water. This narrows the answer choices to either A or B. Step (f) is a reduction, making A the correct answer. The final step is a reduction because the reactant gains two C-H bonds, an indicator of reduction (gaining C-O bonds indicates oxidation; losing C-H bonds indicates oxidation; losing C-O bonds also indicates reduction). It can also be seen that NADPH is oxidized to NADP + . Because NADPH is reacting with the product of Step (d) it is impossible for both species to be oxidized

Using the NADH and FADH2 equivalents given above, demonstrate for the complete oxidation of one glucose molecule where each high energy molecule is created and how they add up to 36 ATP per glucose (HINT: Two common errors are 1) not considering the "net" ATP from glycolysis and 2) ignoring the ATP required for the transport of NADH into the mitochondria).

The overall reaction for glycolysis is: glucose + 2 NAD+ + 2Pi + 2ADP → 2 pyruvate + 2ATP + 2NADH + 2H+ The overall reaction for the citric acid cycle (including pyruvate dehydrogenase) is: pyruvate + 4 NAD+ + FAD + GDP + Pi + 2 H20 → 3 CO2 + 4NADH + 4H+ + GTP + FADH2 Keep in mind that you'll need to double the citric acid cycle equation because glycolysis results in two pyruvates. This means that from complete oxidation of one glucose, we get: NADH = 3 ATP FADH2 = 2 ATP NADH from glycolysis = 2 ATP (because it costs 1 ATP to transport it in) Total, we have (2 x 2) + (8 x 3) + (2 x 2) + 4 = 36 ATPs

What is the difference between an obligate aerobe and a facultative aerobe? Between an obligate and a facultative anaerobe? Which one are you?

The term "obligate" implies that there is no other option, so obligate aerobes must use aerobic respiration and cannot survive without oxygen, while obligate anaerobes must use anaerobic respiration and cannot survive in the presence of oxygen. "Facultative" implies that the organism will use whichever respiration is available. So if oxygen is present, the organism will use aerobic respiration, and if oxygen is absent, the organism will use anaerobic respiration. Facultative anaerobes prefer anaerobic conditions while facultative aerobes prefer aerobic

Glycolysis can be replicated in vitro. If fructose-6-phosphate, ATP, and the enzyme phosphofructokinase are added to a saline solution in a beaker, the addition of a small amount of which molecule will NOT increase the rate of change in the concentration of fructose-1,6-bisphosphate in the beaker? (Assume fructose-6-phosphate is not in excess.) A) AMP B) ATP C) phosphofructokinase D) fructose-6-phosphate

This question requires application of Le Chatelier's principle, but it is even more important to have an understanding of the regulation of glycolysis. Because this is a NOT question, the correct answer must be something that will decrease the rate of formation of the product—or NOT increase it. Answer A is false. Adding AMP is a signal to glycolysis that energy reserves are low and therefore AMP acts as an allosteric activator for the key glycolytic enzymes. Answer C is false because this is the enzyme catalyzing the reaction; adding more of it will speed up the reaction. Answer D is false because this is the substrate in this enzyme-catalyzed reaction and therefore adding more of it will increase reaction rate. Answer B is correct. ATP is an allosteric inhibitor of this step of glycolysis, but one does not need to know that specifically. High-energy molecules provide negative feedback to metabolic processes that create ATP, such as glycolysis

In the synthetic scheme shown in Figure 1, carbon 2 of the acetyl-CoA molecule becomes: A) carbon 1 of HS-ACP B) carbon 3 of butanoyl -CoA C) carbon 4 of butanoyl-CoA D) carbon 3 of -hydroxy-butanoyl-CoA

To answer this question, one must carefully examine the structural changes occurring in step (c). The acetyl group attaches to the other reactant, with the loss of CO2, to form -ketobutyrate. The identity of the carbon can be deduced by considering the necessary rearrangement that will result in the formation of CO2 and HS-ACP. Alternatively, if one is familiar with fatty acid biosynthesis it is known that acetyl groups are added to the end of the growing fatty acid chain, meaning the last carbon on the activated acetyl (carbon 2) will become the last carbon o n the product fatty acid. Answer C is therefore correct

How many cycles of β-oxidation will be required to completely oxidize a 14-carbon fatty acid? How many cycles will be required to oxidize a 17-carbon fatty acid?

To determine how many rounds of β-oxidation is required to oxidize an even numbered fatty acid, simply divide the number of carbons by 2 and subtract 1. So for a 14-carbon fatty acid, 6 rounds of β-oxidation are needed. This is because every round cleaves 2 carbons off. At the end, a final round cleaves the 4-carbon fatty acid into two 2-carbon fatty acids, finishing the oxidation. For an odd numbered fatty acid, subtract 1 to get to an even number. Then divide by 2, subtract 1. So for a 17-carbon fatty acid, 7 rounds of β-oxidation are needed (17-1=16. 16/2=8. 8-1=7). This is because every round cleaves off two carbons, but at the end of an odd numbered fatty acid, the final round cleaves the 5-carbon fatty acid into one 2-carbon fatty acid and one 3-carbon fatty acid. If you're unsure how many rounds are needed, simply draw it out quickly, marking through the fatty acid for every cleavage. In this diagram, every red line is a round of β-oxidation.

Tonodenafil is an experimental diet drug designed to prevent the storage of excess food calories as fat by interfering with fatty acid synthesis during the well-fed state. What is an appropriate carrier molecule, and a likely cellular target, respectively, for the administration of Tonodenafil? A) hydrophilic carrier; nucleus B) lipophilic carrier; mitochondrial matrix C) hydrophilic carrier; mitochondrial matrix D) lipophilic carrier; cytosol

To have its effect, the drug must either pass through the cell membrane, which a lipophilic carrier could do, or bind to a surface membrane receptor (which would be required for a polar drug molecule). There is nothing in the stem indicating that a protein receptor for Tonodenafil is known to exist, and thus a hydrophilic carrier is the best choice. Second, fatty aid synthesis occurs in the cytosol. This leaves only Answer D, even if one did not understand the issues of polarity and passage through the cell membrane. All other choices are false because fatty acid synthesis occurs in the cytosol.

Suppose each of the following biomolecules or structures were radioactively labeled and then identified in vivo during normal physiological functioning. In which cellular compartment would each of the following be found in greatest abundance? a) pyruvate, b) oxaloacetate, c) phosphofructokinase-1 (glycolysis enzyme), d) PDH complex, e) phosphoenolpyruvate, f) glycogen synthase, g) pyruvate carboxylase, h) transketolase/transaldolase, i) α-ketoglutarate, j) succinate dehydrogenase, k) ATP synthase, l) carnitine-acylcarnitine translocase, m) fatty acids undergoing β-oxidation, n) citrate, o) ketolysis, p) argininosuccinate (the urea cycle), q) carbamoyl phosphate (the urea cycle), r) citrulline (the urea cycle), s) ornithine (the urea cycle), t) malate.

a) cytosol, b) mitochondrial matrix, c) cytosol, d) mitochondrial matrix, e) cytosol, f) cytosol—primarily of liver cells, and in kidney cortex cells to a lesser degree g) mitochondrial matrix of liver cells/some kidney cells (NOTE: First, pyruvate carboxylase converts oxaloacetate to pyruvate in the matrix, gluconeogenesiss then continues in the cytosol), h) cytosol—primarily of liver cells, i) mitochondrial matrix, j) inner mitochondrial membrane (part of the ETC), k) inner mitochondrial membrane, l) inner mitochondrial membrane, m) mitochondrial matrix (fatty acids are activated in the cytosol, and very long chain fatty acids are oxidized first in peroxisomes, so you might find traces of radioactivity there, but the question asks for where it will be in abundance, which would be in the matrix), n) mitochondrial matrix, o) mitochondrial matrix of cells throughout the body during fasting or starvation, but NEVER In the liver—it lacks the necessary enzymes (ketogenesis occurs only in the matrix of liver cells, because the enzymes needed are only found in the matrix), p) cytosol—primarily of liver cells and to some extent in the kidneys (NOTE: This is ONLY true because we specified argininosuccinate, which is the product of a cytosolic enzyme that participates in the urea cycle. Of the five enzymes in the urea cycle, two are mitochondrial and three are cytosolic), q) mitochondrial matrix (from carbamoyl phosphate synthetase 1, one of the two mitochondrial urea cycle enzymes), r) mitochondrial matrix (product of the second mitochondrial urea cycle enzyme) AND the cytosol—citrulline is transported from the matrix to the cytosol as part of the urea cycle, s) BOTH the mitochondrial matrix and the cytosol (ornithine is transported from the cytosol to the mitochondrial matrix as part of the urea cycle), t) BOTH the cytosol and the matrix (malate is part of the TCA cycle in the matrix and participates in the Citrate shuttle in the cytosol).