Biochemistry Final Exam: 220 Questions and Answers, Exams of Biochemistry

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Biochemistry Final Exam (220 Questions And

Answers) 2024-2025 Latest Updated 100 % Pass

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which of the following statements regarding redox potentials and free energy changes is false? (a) in oxidative phosphorylation, the electron transfer potential of NADH or FADH2 is converted into the phosphate transfer potential of ATP (b) the standard reduction potential indicates a substance's tendency to become reduced; the actual reduction potential depends on the concentrations of reactants (c) the more positive the reduction potential, the greater the tendency to accept electrons (become reduced) (d) a reaction with a negative deltaE0' (standard reduction potential) is thermodynamically favorable - Solution (d) a reaction with a negative deltaE0' (standard reduction potential) is thermodynamically favorable research on a respiratory electron transfer chain in a recently discovered (hypothetical) species of bacteria has revealed the presence of a series of reversible electron carriers having the following standard reduction potentials: A (ox) / A (red) E1(volts) = + 0. B (ox) / B (red) E1(volts) = - 0. C (ox) / C (red) E1(volts) = - 0. Which of the following indicates the probably sequence of electron transfer through these carriers in this organism's electron transport chain? (a) A to B to C (b) B to C to A (c) C to B to A (d) A to C to B - Solution (b) B to C to A which of the following statements about ATP synthase is true? (a) the proposed mechanism for proton driven ATP synthesis in the mitochondrion suggests that the catalytic subunits of the enzyme cycle through 2 conformational states (open and tight) (b) ATP is synthesized in the loose conformation (c) as protons are translocated through the F0 component of the enzyme, rotation-induced conformational changes in the F1 component drive the synthesis of ATP from ADP and Pi (d) the catalytic component of the enzyme is embedded in the inner mitochondrial membrane - Solution (c) as protons are translocated through the F0 component of the enzyme, rotation- induced conformational changes in the F1 component drive the synthesis of ATP from ADP and Pi

which of the following statements about ATP synthase is false? (a) it is a large multi-protein enzyme complex involved in oxidative phosphorylation (b) the F1 portion of the enzyme is oriented to the matrix side of the mitochondrion and includes the catalytic subunits of the enzyme (c) it uses the electrochemical gradient to synthesize ATP from ADP and Pi (d) it also serves as a transporter molecule that allows ATP to move from the mitochondrial matrix to the cytosol - Solution (d) it also serves as a transporter molecule that allows ATP to move from the mitochondrial matrix to the cytosol True or False: if false, fix it. the terminal electron acceptor in the electron transfer chain is (ATP synthase). - Solution false ; O True or False: if false, fix it. the respiratory enzymes involved in oxidative phosphorylation are multi-subunit protein complexes that accept and donate electrons in a sequence based on (the relative oxidation- reduction potentials) of the prosthetic groups associated with these complexes. - Solution true True or False: if false, fix it. the transfer of electrons down the electron transfer chain is an (endergonic) process and the energy obtained from this process is used to pump protons against a concentration gradient. - Solution false ; exergonic True or False: if false, fix it. (an electron gradient across the inner mitochondrial membrane) links the oxidation of substrates, such as NADH and FADH2, to the synthesis of ATP from ADP and Pi - Solution false ; proton gradient what is the equation that is used to quantify the standard reduction potential between a redox couple? - Solution deltaEo' = Eo' (e- acceptor) - Eo' (e- donor) deltaGo' = -nF(Eo') or -nF(deltaE) n = # of electrons F = faradays constant (96,485 J/VK) Calculate the change in reduction potential for NADH/NAD+ and Q/QH2 pair. (*use table 15-1 in text) is this a thermodynamically favorable rxn? - Solution deltaEo' = 0.045V + 0.315 = 0.360V

yes, the calculated reduction potential is a (+) value which means that deltaGo' is (-), therefore it is thermodynamically favorable by definition. Calculate the change in reduction potential between cytochrome C1 and oxygen. (*use table 15- in text) Based on the redox values of cytochrome C1 and oxygen, we can predict a flow of electrons from complex ______ to complex ________ in the mitochondrial ETC. - Solution deltaEo' = 0.815V - 0.22 = 0.59V III ; IV what is the malate-aspartate shuttle? - Solution The malate-aspartate shuttle system begins with cytosolic oxaloacetate is reduced to malate for transport into the mitochondria. Malate is then reoxidized into the matrix. The net result is the transfer of "reducing equivalents" from the cytosol to the matrix. Mitochondrial oxaloacetate can be exported back to the cytosol after being converted to aspartate by an aminotransferase. what is the significance of the malate-aspartate shuttle with regard to the NADH produced via glycolysis? - Solution The significance with regard to the NADH produced via glycolysis and other oxidative processes in the cytosol cannot directly reach the respiratory chain. There is no transport protein that can ferry NADH across the inner mitochondrial membrane. Instead, "reducing equivalents" are imported into the matrix by the chemical reactions of systems such as the malate-aspartate shuttle system. briefly describe the structure of ATP synthase and the binding change mechanism by which ATP is synthesized via oxidative phosphorylation. - Solution The structure of ATP synthase is a spherical structure consisting of three ⍺ and three β subunits that are connected via a central stalk to the membrane-embedded c ring. The ⍺ subunit is closely associated with the c ring, and a peripheral stalk containing several subunits links subunit a to the catalytic domain. In the binding change mechanism, each of the three β subunits adopts a different confirmation: open (O), loose (L), or tight (T). The substrates ADP and Pi bind to a loose site, ATP is synthesized when the site becomes tight, and ATP is released when the subunit becomes open. The conformational shifts are triggered by the 120 degree rotation of the 𝝲 subunit. Since each of the three catalytic sites cycles through the three conformational states, ATP is released from one of the three β subunits with each 120 degree rotation of the 𝝲 subunit. describe what is meant by the term "protonmotive force" and explain how it links electron transport to ATP synthesis in mitochondria. - Solution The protonmotive force refers to the energy that is stored in the transmembrane electrochemical gradient that is established when protons from the mitochondrial matrix are translocated across the mito membrane to the intermembrane space. The energy needed to push protons against this concentration gradient comes from the energy generated during electron transfer down the electron transfer chain. The energy that is stored in the proton gradient can be used to drive the synthesis of ATP from ADP and Pi.

what is this the structure of? what are its reactive groups? what does it do? - Solution flavin mononucleotide (FMN) (1) two electrons donated by NADH are picked up by flavin mononucleotide (attach to the Nitrogens in ring, the two pi bonds go away to form 1 in the middle of the N's for FMNH2) (2) this noncovalently bound prosthetic group then transfers the electrons, one at a time, to a second type of redox center, an iron-sulfur center what is this the structure of? what are its reactive groups? what does it do? - Solution iron-sulfur cluster

• these clusters are one-electron carriers
• electrons travel between several Fe-S clusters before reaching ubiquinone; ubiquinone is a two- electron carrier but it accepts one at a time from an Fe-S donor what is this the structure of? what are its reactive groups? what does it do? - Solution the heme group of cytochrome B
• the heme groups of cytochromes undergo reversible one-electron reduction, with the central Fe atom cycling between the Fe3+ (oxidized) and Fe2+ (reduced) states what is this the structure of? what are its reactive groups? what does it do? - Solution ubiquinone and ubiquinol (1) gets one electron at a time from Fe-S clusters (2) complex III transfers electrons from ubiquinol to cytochromes the flow of electrons from reduced compounds like NADH and QH2 to an oxidized compound like O2 is a thermodynamically ____________ process. - Solution favorable what is a standard reduction potential? - Solution - indicates a substance's tendency to become reduced
• the actual reduction potential depends on the concentrations of reactants Electrons are transferred from a substance with a _________ reduction potential to a substance with a ____________ reduction potential. - Solution lower ; higher what does the free energy change for an oxidation-reduction reaction depend on? - Solution the change in reduction potential what is oxidation? - Solution loss of electrons what is reduction? - Solution gain of electrons

what does E0' stand for and mean? - Solution standard reduction potential the affinity of a substance to gain electrons under standard conditions of pressure (1 atm), temp of 25 degrees celsius, pH of 7, and all species present at 1M concentrations what can reduction potential indicate? - Solution a substance's tendency to accept electrons what does a positive delta E0' and negative delta G0' mean? - Solution rxn is thermodynamically favorable what does a negative delta E0' and positive delta G0' mean? - Solution rxn is thermodynamically unfavorable what does complex I do? - Solution transfers electrons from NADH to ubiquinone what does the Q cycle do? - Solution it is mediated by complex III and reduces cytochrome C what does complex IV do? - Solution uses electrons from cyctochrome C to reduce O2 to H2O where does electron transport take place? - Solution the mitochrondrion what does malate-aspartate shuttle do? - Solution - transports reducing agents across the inner mitochondrial membrane

• since NADH produced by glycolysis cannot directly reach the ETC (there is no transporter for NADH), reducing equivalents are imported into the mito matrix by the malate aspartate shuttle what protein imports ADP and exports ATP? - Solution ATP translocase what is Complex I of ETC? what does it do? - Solution - NADH dehydrogenase catalyzes the transfer of a pair of electrons from NADH to ubiquinone
• largest ETC complexes with 45 diff. subunits
• electron transport takes place in peripheral arm (oriented towards mito matrix). this segment contains several prosthetic groups (redox centers) that accept and donate electrons within the enzyme
• part of protein has membrane-spanning alpha helices
• electrons transfer from NADH to FMN, then from FMN to Q
• as electrons are transferred from NADH to ubiquinone, Complex I transfers four protons from the matrix to intermembrane space

Summarize Q Pool Rxns. - Solution (1) succinate dehydrogenase (complex II of ETC) is the same enzyme involved in CAC (b) acyl-CoA dehydrogenase is involved in fatty acid oxidation (an energy generating catabolic pathway that occurs in the mito matrix) (c) cytosolic dehydrogenase is active in the glycerol-3-phosphate shuttle system that oxidizes NAHD in cytosol and passes reducing equivalents into mito inner membrane what is complex III of the ETC? - Solution - also called ubiquinol:cytochrome c oxidoreductase or cytochrome bc

• is a dimer
• each monomer is comprised of 11 subunits, cytochrome b, Fe-S protein, and cytochrome c
• transfers electrons from ubiquinol to the peripheral membrane protein, cytochrome C what is the Q cycle? - Solution (1) QH2 donates one electron to Fe-S protein. this electrons travels to cytochrome c1 to cytochrome c (2) QH2 donates its other electron to cytochrome b. the two protons from QH2 are released into the intermembrane space (3) oxidized ubiquinone diffuses to another quinone-binding site where it accepts the electron from cytochrome b, being a half-reduced semiquinone (4) a second QH2 surrenders its two electrons to complex III and its two protons to intermembrane space. one electron goes to reduced cytochrome c. (5) other electron goes to cytochrome b and then to semiquinone. this step regenerates QH using protons from matrix what are the results of the Q cycle? - Solution - two electrons from QH2 reduce two molecules of cytochrome c
• four protons are pumped into the intermembrane space; two from QH2 in first and second round each for every ___ electrons that pass from ubiquinol to cytochrome c1, _____ protons are translocated to the intermembrane space - Solution 2 ; 4 what is cytochrome C and what does it do? - Solution - small, water-soluble protein, localized to the mito intermembrane space
• transfers one electron at a time from complex III to complex IV

what is complex IV (cytochrome oxidase) and what does it do? - Solution - oxidizes cytochrome C and reduces O

• is a dimer
• each monomer contains 13 subunits, with Cu and heme (a and a3) prosthetic groups
• for every two electrons donated by cytochrome c, two protons are translocated to the intermembrane space what rxn does Complex IV catalyze? - Solution 4 cytochrome c (Fe2+) + O2 + 4H+ (arrow) 4 cytochrome c (Fe3+) + 2 H2O what provides the free energy to synthesize ATP? - Solution the formation of a transmembrane proton gradient during electron transport what contributes to the free energy of the proton gradient? - Solution concentration and charge how much energy is available from electron transport? what does this mean? - Solution deltaG0' = -218.2 kJ/mol this is enough energy to drive the endergonic phosphorylation of ADP to form ATP (deltaG0' = 30.5 kJ/mol) what is a protonmotive force? - Solution - a source of free energy represented by the imbalance of protons
• can drive the activity of an ATP synthase what does rotation-induced conformational changes allow to happen? - Solution ATP synthase to bind ADP and Pi to phosphorylate ADP and to release ATP what determines the rate of oxidative phosphorylation? - Solution the supply of reduced cofactors what is Complex V? - Solution - the protein that taps the electrochemical proton gradient to phosphorylate ADP (also known as ATP synthase) one rotation of the ring translocates _____ protons - Solution 8 what different conformations can alpha-beta subunits form? - Solution open, tight, and loose ADP and Pi bind to the _______ conformation - Solution loose ATP is formed in the _________ conformation - Solution tight

ATP is released in the ________ conformation - Solution open conformational change alters ___________ __________ for adenine nucleotides - Solution binding affinity how is oxidative phosphorylation regulated? - Solution by the availability of reduced cofactors (NADH and QH2) produced by other metabolic processes which transport system moves the acyl group of an activated fatty acid across the mitochondrial inner membrane to undergo beta-oxidation? (a) triacylglycerol shuttle (b) glycerol phosphate shuttle (c) lipoprotein shuttle (d) carnitine shuttle - Solution (d) carnitine shuttle before they are degraded in the beta-oxidation pathway, fatty acids must first: (a) be activated via ester linkage to Coenzyme A (b) undergo an oxidation reaction (c) undergo a reduction reaction (d) be transported back into the cytosol - Solution (a) be activated via ester linkage to Coenzyme A each round of beta-oxidation of a saturated fatty acyl-CoA produces ______ , and one acyl-CoA shortened by 2 carbons (a) 1 NADH, 1 QH2, 1 CO2, 1 acetyl-CoA (b) 1 NADH, 1 QH2, 1 acetyl-CoA (c) 1 NADH, 1 QH2, 2 acetyl-CoA (d) 1 NADH, 1 QH2, 1 H2O, 1 acetyl-CoA - Solution (b) 1 NADH, 1 QH2, 1 acetyl-CoA fatty acid oxidation occurs in the __________ ; fatty acid synthesis occurs in the ____________ (a) mitochondria ; cytosol (b) mitochondria ; lysosome (c) cytosol ; mitochondria (d) cytosol ; ER - Solution (a) mitochondria ; cytosol in the first step of fatty acid synthesis, an enzyme catalyzed ATP dependent rxn step converts acetyl-CoA into _______. (a) propionyl-CoA (b) malonyl-CoA (c) acetoacetyl-CoA

(d) HMG-CoA - Solution (b) malonyl-CoA which protein is used to transfer acetyl-CoA across the mitochondrial inner membrane to undergo fatty acid synthesis? (a) acetate transporter (b) oxaloacetate transporter (c) alpha-ketoglutarate transporter (d) citrate transporter - Solution (d) citrate transporter what pathway supplies the bulk of the NADPH needed for fatty acid synthesis in mammals? (a) CAC (b) pentose phosphate pathway (c) glycolysis (d) light rxns of photosynthesis - Solution (b) pentose phosphate pathway which enzyme is the most important control point for fatty acid synthesis? (a) ATP-citrate lyase (b) 3-ketoacyl-ACP reductase (c) 3-hydroxyacyl-ACP dehydrase (d) acetyl-CoA carboxylase - Solution (d) acetyl-CoA carboxylase which of the following statements about triacylglycerols is false? (a) dietary triacylglycerols are a source of fatty acids, which can be used as metabolic fuel (b) the hydrolysis of triacylglycerols by lipases releases fatty acids from the glycerol backbone (c) triacylglycerols in adipose tissue can serve as a long-term storage form of fatty acids (d) triacylglycerols are highly oxidized molecules - Solution (d) triacylglycerols are highly oxidized molecules check if this is right, study guide 17 and 19 # ketone bodies are produced in the ______ and used by the __________ only under conditions such as a prolonged fast. (a) liver ; brain (b) liver ; skeletal muscle (c) kidneys ; heart (d) kidneys ; brain - Solution (a) liver ; brain indicate if statement best describes the hormone insulin (I) or hormone glucagon (G). secreted by the beta-cells of the pancreas - Solution insulin

indicate if statement best describes the hormone insulin (I) or hormone glucagon (G). increases after a meal - Solution insulin indicate if statement best describes the hormone insulin (I) or hormone glucagon (G). binds to a transmembrane cell receptor that activates a G-protein in liver cells - Solution glucagon indicate if statement best describes the hormone insulin (I) or hormone glucagon (G). activates glycogen phosphorylase - Solution glucagon indicate if statement best describes the hormone insulin (I) or hormone glucagon (G). secreted in response to low blood glucose conentration - Solution glucagon indicate if statement best describes the hormone insulin (I) or hormone glucagon (G). increases the number of GLUT4 transporters on muscle cell membrane - Solution insulin what are the two metabolic priorities that are the basis for the above-mentioned changes in fuel utilization during prolonged fasting and starvation? - Solution (1) to feed the brain (2) to preserve muscle mass briefly explain the metabolic (biochemical) adaptations in fuel utilization during starvation that result in each of the changes. - Solution - As glycogen stores are depleted, muscle switches from burning glucose to burning fatty acids

• Insulin secretion ceases with the drop in circulating glucose, so insulin-responsive tissues are not stimulated to take up glucose. This allows for there to be more glucose available to tissues such as the brain that stores very little glycogen and cannot use fatty acids as fuel
• The liver and kidneys respond by increasing the rate of gluconeogenesis using noncarbohydrate precursors such as amino acids and glycerol. After several days, the liver begins to convert mobilized fatty acids to acetyl-CoA and then to ketone bodies. The gradual switch from glucose to ketone bodies prevents the body from using up its proteins to supply gluconeogenic precursors the integration of metabolism involves inter-organ transport of metabolites. describe the relevant biochemical pathways and the metabolites that travel between muscle and liver cells in the Cori cycle. under what conditions is this cycle active? - Solution during periods of high muscle activity, muscle glycogen is broken down to glucose, which undergoes GLY to produce ATP for muscle contraction. this rapid GLY exceeds the capacity for NADH to be reoxidized via the CAC, so the pyruvate generated by GLY is converted to lactate which is transported to the liver to be converted back to glucose via GNG. the newly synthesized glucose is transported back into muscle to sustain ATP production even when all glycogen has been depleted

diabetes is a metabolic disease. in what ways are the metabolic adaptations that take place in diabetes similar to those in prolonged fasting or starvation? - Solution Diabetes is similar to those in prolonged fasting or starvation in the way that even though there is a lot of glucose in the blood, the liver and muscle cells either perceive a lack of glucose (Type 1 Diabetes) or cannot take up glucose (Type 2 Diabetes). In response to this, the cells will go into "starvation" mode; they will begin to increase fat and protein degradation and increase gluconeogenesis and ketogenesis. in what ways do diabetes and starvation differ? - Solution Diabetes and prolonged fasting or starvation also differ as the long-term effects of hyperglycemia begin to take place. In tissues that do take up glucose, excess glucose gets converted to sorbitol which causes precipitation of lens proteins resulting in opacification, blurred vision and eventually blindness. Accumulation of sorbitol can occur in tissues that accumulate glucose. There is also an increased risk of kidney failure, amputation of extremities, stroke, heart attack, cardiovascular disease (especially damage to small blood vessels like the eyes and kidneys), and nerve damage. what do triacylglycerols contain? - Solution fatty acids attached to a glycerol backbone how do fatty acids feed into the CAC? - Solution fatty acids are broken down (oxidized) into 2C and 3C intermediates that feed into the CAC what happens to fatty acids that are to be degraded? - Solution - activated before they are degraded, activation takes place in the cytosol

• activated fatty acids are acylated to CoA
• rxn is driven by ATP hydrolysis
• they are linked to Coenzyme A and then transported into mitochondria to undergo beta oxidation what do triacylglycerols do for a human? - Solution primary source of fatty acids used as metabolic fuel what is lipoprotein lipase? - Solution an enzyme associated with the outer surface of cells (hydrolysis occurs extracellularly) how are triacylglycerols mobilized? - Solution by hormone sensitive lipases and travel through blood stream via the serum protein albumin each round of beta-oxidation has _________ rxns - Solution 4 where does FA oxidation take place? - Solution in the mitochondria

how do acyl groups enter the mitochondria and why this way? - Solution there is no transport molecule for acyl-CoA, so acyl groups enter mitochondria via shuttle system involving carnitine acyl-CoA is degraded into acetyl-CoA beta-oxidation is a _______ process. - Solution spiral each round of beta-oxidation involves _______ enzyme catalyzed steps that yield ______ acetyl- CoA and ________ acyl-CoA shortened by _______ carbons, which becomes the starting substrate for the next round. ______ rounds of beta-oxidation degrade the C16 FA to _____ molecules of acetyl-CoA - Solution 4 ; 1 ; 1 ; 2 7 ; 8 what are the steps of beta-oxidation? - Solution (1) oxidation of acyl-CoA at the 2,3 position is catalyzed by an acyl-CoA dehydrogenase to yield a 2,3-enoyl-CoA. the two e-'s removed from the acyl group are transferred to a FAD prosthetic group. a series of electron transfer rxns eventually transfers the electrons to ubiquinone (Q) (2) catalyzed by a hydratase which adds the elements of H2O across the double bond produced in the first step (3) hydroxyacyl-CoA is oxidized by another dehydrogenase ; in this case, NAD+ is the cofactor (4) thiolysis, catalyzed by a thiolase and releases acetyl-CoA. the remaining acyl-CoA, two Cs shorter than starting substrate, undergoes another round of the four rxns what does beta-oxidation result in? - Solution ATP production how is beta-oxidation regulated? - Solution by the availability of free CoA (to make acyl CoA), and by the ratios of NAD+/NADH and Q/QH2 (reflecting the state of the Ox Phos system) what does fatty acid synthesis begin with? - Solution carboxylation of acetyl-CoA in the cytosol what does fatty acid synthase do? - Solution catalyzes seven separate rxns to extend a fatty acid by 2 Cs how are newly synthesized fatty acids modified? - Solution elongases and desaturases how are ketone bodies created? - Solution ketogenesis converts acetyl-CoA to small soluble ketone bodies how are acyl chains carried in fatty acid oxidation? - Solution by Coenzyme A

how are acyl chains carried in fatty acid synthesis? - Solution by acyl-carrier protein what do both an acyl-carrier protein (ACP) and Coenzyme A (CoA) have in common? - Solution both ACP and CoA include a pantothenate (vitamin B5) derivative ending with a reactive SH group that can be esterified to an acyl or acetyl group what is different between an acyl-carrier protein (ACP) and Coenzyme A (CoA)? - Solution in CoA, pantothenate group is esterified to an adenine nucleotide. in ACP, it is esterified to a Ser OH group of a polypeptide. In mammals, ACP is part of a larger multifunctional protein, fatty acid synthase. how are acetyl groups moved to the cytosol? - Solution via the citrate transport chain what is the starting material for fatty acid synthesis? how is it generated? - Solution acetyl CoA which is generated in the mitochondrion via PDH what is the donor of the 2C acetyl units used to build a fatty acid? - Solution malonyl-CoA in fatty acid synthesis, acetyl-CoA carboxylase catalyzes the first, 2-step rxn. what are the first 2 steps? - Solution (1) biotin is carboxylated. CO2 as bicarbonate is activated by its attachment to the prosthetic group biotin (2) the carboxyl group is transferred to acetyl-CoA to make malonyl-CoA this is the committed step of FA synthesis how is biotin linked to acetyl-CoA carboxylase? what does this allow biotin to do? - Solution - linked via a lysine residue

• the long flexible arm allows the biotin to translocate between the 2 active sites of the enzyme fatty acid _________ catalyzes fatty acid __________ - Solution synthase ; synthesis what are the first two steps of FA synthesis? - Solution (1) the 2C acetyl group that will be lengthened is transferred from CoA to a Cys side chain of fatty acid synthase (2) the malonyl group that will donate an acetyl group to the growing fatty acyl chain is transferred from CoA to the ACP domain of the enzyme what are the condensation steps of FA synthesis? - Solution (3) in this condensation rxn, the malonyl group is decarboxylated and the resulting 2C fragment attacks the acetyl group to form a 4C product (4) the 3-ketoacyl product of step 3 is reduced

(5) dehydration introduces a 2,3 double bond (6) a second NADPH-dependent rxn completes the conversion of the condensation product to an acyl group (7) the acyl group is transferred from ACP to the enzyme Cys group and another malonyl group is loaded onto the free ACP, ready for another condensation rxn what occurs after the condensation steps in FA synthesis? - Solution (8) all of the steps prior are repeated 6 times to build a C16 fatty acid (9) a thioesterase hydrolyzes the thioester bond to release palmitate what is important about palmitate? - Solution it is the most common product of FA synthesis in mammals where does NADPH come from? - Solution pentose phosphate pathway why is the synthesis of one molecule of palmitate a "good investment"? - Solution 7 rounds of fatty acid synthesis costs 42 ATP (7 ATP in the production of 7 malonyl CoA) and 14 NADPH (14 x 2.5 = 35 ATP) in steps 4 and 6 of each round, however oxidizing one palmitate yield much more E, so it is considered a good investment how do you control fatty acid metabolism? - Solution - under conditions of abundant fuel, the products of carbohydrate and amino acid metabolism are directed toward FA synthesis and the resulting FAs are stored in triacylglycerols in adipose tissue

• acetyl-CoA carboxylase is inhibited by the pathway product, palmitoyl CoA and activated by citrate (which signals a lot of acetyl-CoA)
• malonyl CoA inhinits the carnitine transporter; consequently, when FA synthesis is underway in cytosol, no acyl groups are transported into mito to undergo beta-oxidation. this prevents wasteful simultaneous activity of FA synthesis and breakdown what is acetyl-CoA carboxylase? - Solution the enzyme that catalyzes the committed step in FA synthesis what are the differences between FA synthesis and beta-oxidation? - Solution in mammalian cells:
• in beta-oxidation, the acyl group is attached to CoA; in FA synthesis, the growing acyl chain is bound by an acyl carrier protein (ACP)
• beta-oxidation takes place in mito ; FA synthesis occurs in cytosol

• beta-oxidation funnels electrons to NAD+ and Q; in FA synthesis, NADPH is the source of reducing power acetyl-CoA can also form... - Solution ketone bodies during a prolonged fast, how do tissues meet their E needs? - Solution when glucose is unavailable from diet and liver glycogen has been depleted, many tissues depend on FAs released from stores triacylglycerols to meet E needs what part of the body does not use FAs and why? - Solution the brain does not use FAs because they pass poorly through the blood brain barrier (permeability barrier that prevents certain substances from entering brain extracellular fluid in the CNS) what is used to source fuel for the brain during a prolonged fast? - Solution GNG helps to meet brain's E needs, but liver also produces ketone bodies (acetoacetate and 3-hydroxybutyrate) as a fuel source brain what are the steps to ketogenesis (the production of ketone bodies)? - Solution (1) 2 molecules of acetyl-CoA condense to form acetoacetyl-CoA. the rxn is catalyzed by a thiolase which breaks a thioester bond (2) the 4C acetoacetyl group condenses with a third molecule of acetyl-CoA to form the 6C 3- hydroxymethylglutaryl-CoA (HMG-CoA) (3) HMG-CoA is degraded to the ketone body acetoacetate and acetyl-CoA (4) acetoacetate undergoes reduction to produce another ketone body, 3-hydroxybutyrate (5) some acetoacetate may also undergo nonenzymatic decarboxylation to acetone and CO Ketones are.... (3 answers) - Solution - small
• water soluble
• can cross BBB during period of high ketogenic activity, such as occurs in diabetes, ketones may be produced __________ than they are _____________. - Solution faster ; consumed what can happeh when ketones are produced faster than they are consumed? what are the symptoms? - Solution ketoacidosis (acidification of the blood) nausea, vomiting, confusion, coma, and even death if left untreated what is the job of ketones produced in the liver? - Solution they are transported out to other tissues to be used as fuel

why can't the liver metabolize ketones? - Solution it lacks 3-ketoacetyl CoA transferase what are the steps to the catabolism of ketone bodies? - Solution (1) 3-hydroxybutyrate is oxidized back to acetoacetate (2) succinyl-CoA donates its CoA group to produce acetoacetyl-CoA (3) thiolase then uses a free CoA group to cleave the 4C unit to two molecules of acetyl-CoA in mammalian cells, most metabolic rxns take place in either the ___________ or the _____________ ___________. - Solution cytosol ; mitochondrial matrix what are ways metabolism can be regulated? - Solution - compartmentation of opposing processes

• organs being specialized for diff. functions how much and where are triacylglycerols stored? - Solution adipose tissues stores about 95% of the body's triacylglycerols what do muscles store and can it use as a fuel source? - Solution - stores glycogen
• can use glucose, fatty acids, or ketone bodies as a fuel source what does the heart prefer as a fuel source? - Solution fatty acids what can kidneys do? - Solution helps dispose of nitrogen and can produce glucose via GNG how can the metabolic functions of a tissue change? - Solution it depends on the body's metabolic state (i.e. immediately following a meal or after many hours of fasting) what is the warburg effect? - Solution many cancer cells exhibit high rates of glycolysis what is the circulatory system? - Solution the means by which metabolites made in one organ can be transported to another what is the Cori cycle? - Solution transport of lactate from muscle to liver what is the glucose-alanine cycle? - Solution - pyruvate is produced by muscle glycolysis
• pyruvate is trans-aminated to make alanine
• alanine is transported from the muscle to the liver

what are the steps of the Cori cycle? - Solution (1) during period of high muscle activity, muscle glycogen is broken down to glucose which undergoes GLY to produce ATP for muscle contraction. (2) this rapid GLY exceeds the capacity for NADH to be reoxidized via the CAC, so the pyruvate generated by GLY is converted to lactate, which is transported to the liver to be converted back to glucose via GNG (3) the newly synthesized glucose is transported back into muscle to sustain ATP production even when all glycogen has been depleted what are the steps of the glucose-alanine cycle? - Solution (1) during vigorous exercise, muscle protein breaks down and the resulting amino acids undergo transamination to yield an alpha- ketoglutarate which boosts the activity of the CAC and alanine is transported to liver (2) amino group is used for urea synthesis and the resulting pyruvate is converted to glucose (via GNG) and transported back to the muscle to be used as a fuel source pancreatic cells release ___________ in response to _____________ _____ _________________ ___________________. - Solution insulin ; increases in circulating glucose insulin stimulates.... - Solution the uptake of glucose and the storage of metabolic fuels what promotes glycogenolysis and lipolysis? - Solution glucagon and epinephrine what regulates appetite and fuel metabolism? - Solution hormones produced by adipose tissue and digestive organs what does AMP-dependent protein kinase activate and inhibit? - Solution activates ATP- producing pathways, inhibits ATP-consuming pathways what do hormones affect? - Solution fuel metabolism insulin is released...... and promotes..... - Solution released in response to an increase in blood glucose and promotes glucose uptake in cells what are insulin and glucagon produced from? - Solution pancreatic islets what do pancreatic islets consist of? - Solution beta cells which produce insulin and alpha cells that produce glucagon most pancreatic tissues produce.... - Solution digestive enzymes what is released in response to glucose? what triggers it? - Solution insulin

glucokinase appears to be a glucose sensor, triggering insulin release at physiological conditions, hexokinase is _____________. - Solution saturated what varies with glucose concentration? - Solution glucose phosphorylation by glucokinase after a meal, the blood glucose concentration. ________. this ________________________. - Solution increases from about 4-6 mM to about 8 mM increase triggers the release of insulin what does glucokinase do in glycolysis? - Solution in liver and pancreatic beta cells, a special isozyme of hexokinase called glucokinase catalyzes the first step in glycolysis what is different between hexokinase and glucokinase? - Solution glucokinase is maximally sensitive to changes in blood glucose concentration and it is believed that activation of glycolysis by glucokinase after a meal is what stimulates insulin release from the pancreas what cells can respond to the hormone insulin? - Solution only cells that bear insulin receptors can respond to the hormone insulin and the cell's response is tissue specific how does insulin stimulate glucose uptake in muscle and adipose tissue? - Solution insulin stimulates glucose uptake several fold by increasing the number of glucose transporters at the cell's surface. these specialized glut4 transporters (which are different from other glucose transport proteins) are situated in the membranes of intracellular vesicles insulin triggers... - Solution vesicle fusion to the plasma membrane when the insulin stimulus is removed, ________________________________. - Solution endocytosis returns the transporters to intracellular vesicles hormones are ____________ signals that induce ______________ responses. - Solution extracellular ; intracellular a ______________ (ligand) binds to a _____________ (receptor) that is embedded in the _______ ______________. - Solution hormone ; protein ; cell membrane what happens when a hormone binds to a protein? - Solution it induces a conformational change that activates the receptor, allowing it to then interact with and activate other intracellular molecules insulin binding activates ..... - Solution a receptor tyrosine kinase signal transduction pathway what happens when a ligand binds to a RTK? - Solution it triggers a series of cellular responses by phosphorylating many intracellular target proteins. the extracellular signal is amplified as it is transduced in the cell.

what does the insulin receptor consist of? - Solution 2 alpha and 2 beta subunits joined by disulfide bonds the extracellular alpha subunits bind insulin at 2 possible sites and the beta subunits each include a membrane-spanning segment and cytoplasmic tyrosine kinase domain what occurs when insulin binding induces a conformational change? (activation of the insulin receptor tyrosine kinase) - Solution it facilitates autophosphorylation at 3 Tyr residues the ligand induced conformational change in the RTK brings its 2 tyrosine kinase domains close enough so that they can phosphorylate (activate) each other. the phosphorylated RTK activates other intracellular kinases, which in turn phosphorylate (to activate or inhibit) many other target proteins in the cell (i.e. the original extracellular signal is amplified) how does insulin promote fuel use and storage? - Solution it signals the 'fed' state (i.e. fuel abundance) and decreases the metabolism of stored fuel and promotes fuel storage what is metabolic effect of insulin on muscle and other tissues? - Solution - promotes glucose transport into cells

• stimulates glycogen synthesis
• suppresses glycogen breakdown what is metabolic effect of insulin on adipose tissue? - Solution - activates extracellular lipoprotein lipase
• increases level of acetyl-CoA carboxylase
• stimulates triacylglycerol synthesis
• suppresses lipolysis what is metabolic effect of insulin on the liver? - Solution - promotes glycogen synthesis
• promotes triacylglycerol synthesis
• suppresses gluconeogenesis how is glucagon synthesized and released? - Solution - is a 29 AA peptide hormone that is synthesized by alpha cells of the islets of Langerhans in the pancrease
• released when blood glucose concentrations drop below 5 mM what hormones are synthesized in the adrenal (suprarenal) glands? - Solution epinephrine (adrenaline) and norepinephrine (noradrenaline) what does the three hormones glucagon, epinephrine, and norepinephrine do and what does it affect? - Solution they affect fuel metabolism. all three bind to transmembrane receptors on the cell surface that activate G proteins, which then activate intracellular adenylate cyclase to produce the second messenger cAMP

where does signal transduction by glucagon, epinephrine, and norepinephrine occur? - Solution through g-protein receptors what is different between insulin versus glucagon and epinephrine? - Solution in contrast to insulin, glucagon (in liver and adipose cells) and epinephrine (in muscle cells) promote the mobilization and catabolism of stored fuel molecules what allows for the reciprocal regulation of glycogen metabolism? - Solution covalent modification via phosphorylation and dephosphorylation glucagon dependent kinases ___________________ (activate) ______________ _____________ (degradation) and _________________ (deactivate) ______________ ______________ (synthesis). - Solution phosphorylate ; glycogen phosphorylase ; phosphorylate; glycogen synthase insulin dependent phosphatases ____________________ (deactivate) _________ ______________ and _______________ (activate) ______________ _______________. - Solution dephosphorylate ; glycogen phosphorylase ; dephosphorylate; glycogen synthase what is the source and action of the following hormone? adiponectin - Solution adipose tissue ; activates AMPK (promotes fuel catabolism) what is the source and action of the following hormone? leptin - Solution adipose tissue ; signals satiety what is the source and action of the following hormone? resistin - Solution adipose tissue ; blocks insulin activity what is the source and action of the following hormone? neuropeptide Y - Solution hypothalamus ; stimulates appetite what is the source and action of the following hormone? cholecystokinin - Solution intestine ; suppresses appetite what is the source and action of the following hormone? incretin - Solution intestine ; promotes insulin release and inhibits glucagon release what is the source and action of the following hormone? PYY(3-36) - Solution intestine ; suppresses appetite

what is the source and action of the following hormone? amylin - Solution pancreas ; signals satiety what is the source and action of the following hormone? ghrelin - Solution stomach ; stimulates appetite how does AMP-dependent protein kinase act as a fuel sensor? - Solution - cell's "fuel gage"

• monitors levels of AMP/ADP/ATP
• AMP and ADP, representing the cell's need for energy, activate AMPK; ATP, representing energy sufficiency, inhibits AMPK
• AMPK responds to hormones such as leptin and adiponectin
• AMPK activation switches off ATP-consuming anabolic pathways and switches on ATP- generating catabolic pathways what is the effect of AMP-dependent Protein Kinase on... hypothalamus - Solution increases food intake what is the effect and response of AMP-dependent Protein Kinase on... liver - Solution - increases glycolysis
• increases FA oxidation
• decreases glycogen synthesis
• decreases gluconeogenesis what is the effect and response of AMP-dependent Protein Kinase on... muscle - Solution - increases FA oxidation
• increases mitochondrial biogenesis what is the effect and response of AMP-dependent Protein Kinase on... adipose tissue - Solution - decreases FA synthesis
• increases lipolysis

what does the body break down during starvation? what does it generate? - Solution - breaks down glycogen, fats, and proteins

• generates glucose, FAs, and ketone bodies what does obesity result from? - Solution metabolic, environmental, and genetic factors what leads to hyperglycemia in diabetes? - Solution either a lack of insulin or the inability to respond to it what is the metabolic syndrome characterized by? - Solution - obesity and insulin resistance
• high visceral fat surrounding the abdominal organs which produces less leptin and adiponectin (hormones that increase insulin sensitivity) and more resistin (promotes insulin resistance) most tissues in the body use _______ as their preferred fuel and turn to ____ _______ only when the glucose supply diminishes. except in the intestines, ______ ______ are not a primary fuel. - Solution glucose ; FAs amino acids how long can an average adult survive a famine? why? - Solution - can survive a famine lasting up to a few months
• an adaptation likely shaped by seasonal food shortages during human evolution what is the first priority for metabolic adaptations during starvation? - Solution to feed the brain how does the body feed the brain during starvation? - Solution - liver and muscle cells store less than a day's supply of glucose in the form of glycogen
• as glycogen stores are depleted, muscle switches from burning glucose to FAs
• with decrease in blood glucose, insulin secretion stops and insulin responsive tissues stop taking up glucose
• this leaves remaining glucose available for the brain, which can not use FAs as fuel what is the second priority for metabolic adaptations during starvation? - Solution to preserve muscle mass how does the body preserve muscle mass during starvation? - Solution - liver and kidneys respond to continued demand for glucose by increasing GNG using amino acids from protein degradation and glycerol from FA breakdown

• after several days of fasting, liver begins to convert mobilized FAs to acetyl-CoA abd then to ketone bodies, to be used primarily by brain and heart tissue
• switch from glucose to ketone bodies after prolonged fasting prevents the body from depleting its proteins to supply GNG precursors what happens to FAs, ketones, and carbohydrates during a 40-day fast? - Solution FAs - concentration in blood increases about 15-fold ketones - concentration in blood increases about 100-fold carbohydrates - concentration in blood decreases no more than 3-fold what are the factors impacting obesity and consequences? - Solution impact:
• diet
• metabolism
• environmental
• genetic consequences:
• cardiovascular disease
• diabetes
• cancer what does the hormone leptin do in terms of the weight of the human body? - Solution establishes the set point set point is the body weight that remains relatively constant and independent of energy intake and expenditure the lack of what hormone can result in obesity? - Solution - the absence of leptin or from leptin resistance can result in obesity due to a defect in the leptin signaling pathway
• this makes leptin less effective in suppressing appetite, causing weight gain when an individual gains weight, how does this affect the set point? - Solution the increase in adipose mass succeeds in signaling appetite satisfaction (due to increased leptin), but this now results in a higher set point at a higher body weight, making it difficult to lose weight fuel oxidation occurs... - Solution in the absence of ATP generation what are some side effects of diabetes? - Solution - excrete large amounts of sugar in their urine
• frequent urination

• uncontrolled thirst
• lack of energy
• weight loss what is type 1 diabetes? - Solution an autoimmune disease in which pancreatic beta cells are destroyed what is type 2 diabetes? - Solution - 95% of all cases
• characterized by insulin resistance what is the difference between type 1 and type 2 diabetes? - Solution liver and muscle cells either: type 1 - perceive a lack of glucose type 2 - can't take up glucose why can diabetes by biochemically characterized as "starvation in the midst of plenty"? - Solution even though there is a lot of glucose in the blood, liver and muscle cells either perceive a lack of glucose or can't take up glucose. in response, the cells go into starvation mode. what does it mean when cells go into starvation mode? - Solution - increase fat and protein degradation
• increase gluconeogenesis and ketogenesis what are the long term consequences of hyperglycemia? - Solution - in tissues that take up glucose, excess glucose is converted to sorbitol which can cause precipitation of lens protein resulting in opacification, causing blurred vision and eventually blindness
• accumulation of sorbitol in tissues that do accumulate glucose
• cardiovascular disease, especially damage to small blood vessels (eyes and kidneys), nerve damage
• increased risk of kidney failure, amputation of extremities, stroke, and heart attack what is an example of this class of antidiabetic drugs and what is the mechanism of action? biguanides - Solution metformin (glucophage)
• stimulates AMPK
• reduces glucose release from liver
• increases glucose uptake by muscle

what is an example of this class of antidiabetic drugs and what is the mechanism of action? sulfonylureas - Solution glipizide (glucotrol)

• blocks a K+ channel in beta cells
• leading to increased production and secretion of insulin what is an example of this class of antidiabetic drugs and what is the mechanism of action? thiazolidinediones - Solution rosiglitazone (avandia)
• binds to peroxisome proliferator-activated receptors to activate gene transcription
• increases insulin sensitivity how does the metabolic syndrome link diabetes and obesity/insulin resistance? - Solution obesity: in diabetes, the body acts as if it were starving. paradoxically, about 80% of patients with type 2 diabetes are obese and obesity is strongly correlated with the development of the disease high levels of dietary fats can lead to fat toxicity -
• fat accumulation in muscle and adipose tissue
• impairment of glut4 translocation and decreased glucose uptake
• increased gluconeogenesis in liver, contributing to hyperglycemia
• increased insulin secretion causing beta-cell exhaustion Insulin resistance: metabolic syndrome can be characterized by high visceral fat which produces less leptin and adiponectin and more resistin what can improve symptoms of metabolic syndrome? - Solution weight loss