BIOCHEMISTRY 102 FINAL EXAM NOTES 5/30/08 The final exam will be approximately 300 points, and will be divided into roughly 200 points from weeks 7-10 and 100 points from weeks 1-6. The following list gives you a specific description of the areas that will be covered in the final from weeks 7 to 10 of the class, and identifies the relevant portions of the 1st and 2nd midterm exam notes that will be covered in the final. 1. Some problems from Problem Sets 7-10, or slight variations on these problems, may be on the exam. 2. A number of questions will be based on the concepts, explanations, and important facts presented in lecture during weeks 7-10. Some (but not all) of these concepts, explanations, and facts are noted below. 3. Know the sequence of reactions, structure of each molecule, use of ATP, NAD, FAD, NADPH, etc., and subcellular localization (cytosol, inner mitochondrial membrane, mitochondrial matrix, etc.) for the following: (a) Amino Acid Catabolism: Be able to reproduce the reactions which convert a dietary amino acid to an a keto acid (transamination with production of glutamate from aKG) and the oxidative deamination reaction which converts glutamate to aKG plus NH4+ (glutamate dehydrogenase) (that is, know the reactions at the top of handout #25). Be able to reproduce the carbamoyl P synthetase reaction and all reactions of the urea cycle (see lecture handout # 27). Know that 18 of the a keto acids from the 20 common amino acids either already are, or can be converted to, a TCA cycle intermediate or pyruvate (and so can be used for glucose synthesis). Know the overall cost of excreting nitrogen as urea rather than as NH4+ (4 ATP equivalents per urea) and why terrestrial vertebrates needed to evolve the energetically expensive urea synthesis pathway for nitrogen disposal while fish excrete NH4+ directly through their gills. Know the advantage to reptiles and birds of excreting nitrogen as uric acid, a compound that requires even more ATP equivalents to produce than does urea. (b) Gluconeogenesis: synthesis of new glucose in the liver starting from pyruvate or any TCA cycle intermediate in the mitochondrial matrix and ending with free glucose in the cytosol. Know the net consumption of ATP required to drive glucose synthesis from two lactate molecules (6 ATP). Know that pyruvate and TCA cycle intermediates for gluconeogenesis are obtained mainly from the catabolism of body protein (mostly muscle). (c) Glycogen synthesis: synthesis of glycogen from glucose-6-P in the cytosol, including the point on the (glucose)n polymer (i.e., the 4 OH group) to which carbon one of the entering glucose attaches. Know the number of net ATP equivalents driving this incorporation (1 ATP). (d) Fatty acid biosynthesis (FAB) starting with 2 acetyl CoA in the cytosol and ending with the formation of CH3CH2CH2C(O)-S-ACP. (see handout #36). Know that 14 NADPH, 7 ATP, and 8 acetyl CoA molecules are required for the synthesis of palmitate. Know that all intermediate stages in the synthesis of palmitate by fatty acid synthase remain covalently attached to the complex, and that the hydrolase activity of the complex cleaves the palmitoyl--SACP bond to release free palmitate from the complex. You should know the advantages of the fatty acid synthase design (catalytic efficiency, because the concentration of each intermediate remains bound to the complex at a high local concentration; synthetic efficiency, because no product is released prior to palmitate, the minimum length fatty acid to form a membrane bilayer). You should also know that FAB is most active in adipose tissue, liver, and lactating mammary tissue, and that the acetyl CoA required for FAB come from glucose catabolism. (e) Source of acetyl CoA for FAB. You should know that the acetyl CoA molecules used for FAB in the cytosol are generated by PDH in the matrix, and that there is no translocase that enables acetyl CoA to pass across the inner mitochondrial membrane. You should be able to reproduce the three steps needed to transfer the acetyl CoA from matrix to cytosol (citrate synthase in matrix, citrate translocase, citrate lyase in cytosol; handout #38). You do not need to know the steps that return OAA from cytosol to matrix. (f) Pentose phosphate pathway: You should know that the primary function of the pentose phosphate pathway is to produce NADPH for biosynthetic reactions such as fatty acid biosynthesis, and that thepathway is most active in tissues with the highest rate of fatty acid biosynthesis. You should know that the pathway also produces ribose for nucleic acid biosynthesis. You should be able to reproduce the oxidative branch of the pentose phosphate pathway (= the phosphogluconate pathway; see lecture handout 33). You do not need to memorize the non-oxidative branch of the pentose phosphate pathway, but you should know that the function of the non-oxidative branch is to convert the product of the oxidative branch (ribose-5-P) into intermediates in the glycolytic reaction sequence (F6P & G3P). You should also know that the non-oxidative branch requires transaldolase and transketolase. 4. Know the definition of the committed step in a metabolic pathway and know that the strategic objective of the reciprocal regulation of biosynthetic pathways (e.g., gluconeogenesis) and biosynthetic pathways (e.g., glycolysis) is to ensure that both pathways are not active at the same time, a process that would simply waste ATP energy in a ‘futile cycle’. Know the regulation of the following pathways: (a) Fatty acid biosynthesis: regulation at committed step (acetyl CoA carboxylase): allosteric inhibition by, palmityl CoA (an example of feedback inhibition at the committed step) and allosteric activation by citrate (a signal of the availability of acetyl CoA for FAB). Covalent regulation: Protein kinase A phosphorylates and thereby inactivates acetyl CoA carboxylase. (b) Urea cycle: short term-- carbamoyl phosphate synthetase I is allosterically activated by N-acetylglutamate, a signaling molecule whose level is elevated whenever the concentration of glutamate in liver cells is high, as could occur after a meal rich in protein. Long term: the effect of a prolonged high protein diet is to elevate the concentration of all urea cycle enzymes in the liver. (c) Glycogen synthase (GS): conversion from active GSa to inactive GSb by the protein kinase A-dependent
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