PHA 6958 Biochemistry

I'm working on a biochemistry multi-part question and need an explanation and answer to help me learn.

Questions 1 thru 13 are worth 3 points each, question 14 is worth 5 points, and questions 15 and is worth 6 points.

• Why is the glycolytic pathway central to cell metabolism, and which step in the glycolytic pathway is the committed step?
• Describe the 3 pathways of pyruvate metabolism.
• Why are phosphorylated intermediates of glycolysis important? What specifically are the functions of the phosphoryl groups of these intermediates?
• Under what conditions is phosphofructokinase 1 activated, and under what conditions is it inactivated?
• What is a kinase? Provide 3 examples wherein a kinase is important in the metabolic pathway.
• What is galactosemia? How does it occur, and what are the symptoms?
• Under what conditions is lactate formed? Is there a net change in the oxidation state of carbon when glucose is converved to lactate through two oxidation-reduction steps?
• Laypersons often use the term "oxygen debt". Using your text and any available web resources, briefly explain oxygen debt in biochemical terms.
• D-fructose can undergo glycolysis after being phosphorylated and cleaved to glyceraldehyde and dihydroxyacetone phosphate. What source of D-fructose would humans most commonly encounter?
• There are two end products of the oxidative reactions of the pentose phosphate pathway. Name them and identify an end point for each, i.e. what roles these two products might eventually play.
• True or False:
  • The pentose phosphate pathway generates NADPH+ H⁺ to be used for fatty acid synthesis. T/F
  • The oxidative phase of the pentose phosphate pathway is reversible. T/F
  • The nonoxidative phase is reversible. T/F

• In figure 14-21 note that phosphopentose isomerase catalyzes the reaction which ends in the product D-Ribose 5-phosphate. In plant systems, the enzyme phophopentose epimerase is encountered. This would catalyze Ribulose 5-phosphate to yield ____________________?
• In the nonoxidative reactions of the pentose phosphate pathway, transketolase is a TPP-dependent enzyme. What is TPP (literally and functionally), and what would happen in the pathway if no TPP was available?
• Glucose is the primary and preferred source for energy for and during normal central nervous system activity.
  What types of physiological conditions might create a biochemical environment whereby lactate would be preferred over glucose? Read the following article to aid in formulating your answer: Bliss TM and Sapolsky RM . (2001) Brain Research, 899 (1,2): 134-141.
• Locate and read the following article: Liang Q, Donthi RV., Kralik, PM, and Epstein PN. (2002) Cardiovascular Research , 53 (2): 423-430. Propose an explanation as to why the glycogen content of the hearts of the transgenic mice was elevated. What enzyme also demonstrated increased levels?

Questions 1 thru 14 are worth 3 points each; questions 15 and 16 are worth 4 points each.

• With respect to thermodynamics, why can biosynthetic pathways not be simply considered the reverse of corresponding catabolic pathways?
• Compare the net equations of glycolysis and gluconeogenesis and explain why the synthesis of glucose is so costly.
• Why is the biosynthesis of glucose so important in mammals?
• List the following:
  • Most common precursors for glucose biosynthesis
  • Organs which use glucose as their primary energy source
  • Organs or tissues where gluconeogenesis takes place

• Explain in detail how both glycolysis and gluconeogenesis can be irreversible cellular processes.
• What drives the conversion of fructose 1, 6- bisphosphate to fructose 6 -phosphate?
• Describe the role of malate transport in gluconeogenesis.
• How does fatty acid oxidation contribute to gluconeogenesis? Under what conditions do amino acids get converted to glucose?
• What are the effects of G6P, F1,6-BP, F2,6-BP on glycolysis and gluconeogenesis?
• What are the effects of cAMP, AMP, ATP, citrate and acetyl-CoA on glycolysis and gluconeogenesis?
• How many ATP equivalents are required to synthesize a glucose from two pyruvate in order to bypass the irreversible steps in glycolysis?
• Why are sugar nucleotides suitable for biosynthetic reactions?
• How does F2,6-BP control the conversion of F6P to F1,6-BP or the reverse?
• In the final stages of gluconeogenesis, glucose-6-phosphatase converts glucose-6-phosphate to free glucose and inorganic phosphate. Where does this occur?
• Read the article below. This study addresses the synthesis of a trisaccharide that humans do not metabolize. Why are studies such as this and others which examine bacterial systems for enzymatic activity on carbohydrates ultimately beneficial to addressing human health concerns?
  Perrin V, Fenet B, Prally J, Lecroix F, and Ta CD. (2000) Carbohydrate Research, 325 (3): 202-210.
• Hepatocytes are an important model for in vitro study of metabolism. Read the article below and describe how the supplementation of cell culture media with amino acids and hormones affected the activity of hepatocytes and the occurrence of futile cycles. Chan C, Berthiaume F, Lee K, and Yarmush M. (2003) Metabolic Engineering, 5 (1): 1-15.

• Describe the structure of coenzyme A focusing on the components of the molecule. What is its function? [2]
• Why are thioesters good donors of acyl groups? What exactly are thioesters? [2]
• What is the source of energy for steps 1 through 3 of the overall pyruvate dehydrogenase complex reaction? [2]
• Describe how the different enzyme subunits of pyruvate dehydrogenase interact with their cofactors to catalyze decarboxylation of pyruvate. [3]
• How is the pyruvate dehydrogenase complex regulated through covalent modification? [3]
• What function do the lipolysyl moieties of the second enzyme in the pyruvate dehydrogenase complex serve? [2]
• What is the overall purpose of the citric acid cycle, and where do its reactions take place in eukaryotic organisms? [2]
• What is the net energy yield per molecule of glucose for the combined reactions of glycolysis, the pyruvate dehydrogenase reaction and the citric acid cycle? [2]
• Under what circumstances is pyruvate carboxylase activity stimulated? [2]
• Why is citrate synthase a good candidate for a regulatory enzyme? [3]
• Define the term amphibolic pathway and explain how the Citric Acid Cycle meets the criteria. [2]
• Which steps of the Citric Acid Cycle are irreversible? [2]
• Name an alternative fate of succinyl-CoA in the absence of succinyl-CoA synthetase. [2]
• What is meant by the term substrate-level phosphorylation? At what step of the Citric Acid Cycle does this play a role? [3]
• Oxidation of isocitrate and alpha-ketoglutarate release carbon atoms and thus produce energy. How is this energy conserved for later use in the cycle? [2]
• Fumarate is converted to malate through ______________________
  • oxidation
  • hydration
  • hydrolysis
  • phosphorylation

Is this conversion stereospecific? Y / N [2]

• What is the fate of oxaloacetate in the liver? [2]

• Explain why the coordinated regulation of isocitrate lyase and isocitrate dehydrogenase is advantageous to an organism. [4]
• Adipose tissue utilizes acetate to synthesize triglycerides. Why can cells not use acetate as a precursor for synthesizing glucose, as is seen in plants, bacteria and fungi? [3]
• Using the web and your UF library resources, identify a disorder or disease associated with deficiency of one of the regulatory enzymes or co-factors of the Citric Acid Cycle. Describe the symptoms of the disorder/disease and how it might be treated, if at all. [5]

Questions 1 thru 11 are worth 3 points each, 12 thru 14 are worth 4 points each, and question 15 is worth 5 points.

• Solubilization of dietary lipids, achieved by mixing bile salts and degrading them with pancreatic lipases, is required for transport across the intestine where the free fatty acid and the lysophospholipid can then be resynthesized into triacylglycerols in the intestinal mucosal cells. Why is this necessary?
• Describe how and why the above differs from the transport of fatty acids into the mitochondria?
• Fatty acid oxidation occurs in the mitochondrial matrix. In review, where did the oxidative catabolism of glucose take place?
• How are triacylglycerols functionally sequestered within adipose cells prior to a hormonal signal which causes them to be released into the bloodstream?
• Explain in detail how different types of lipids are transported in blood to AND from adipose tissue.
• What is the energetic cost of fatty acyl-CoA formation and where does this fatty acid activation take place?
• Explain the roles of the two pools of coenzyme A and the processes utilized to keep these pools separate.
• What types of reactions make up the 4 basic steps of β-oxidation?
• Describe the enzyme complexes that receive electrons form the reduced electron carriers.
• How many molecules of ATP are generated by the reoxidation of each type of electron carrier?
• Compare saturated and unsaturated fatty acid oxidation with respect to the amount of ATP formed.
• Explain how odd-chain fatty acid oxidation differs from even chain fatty acid oxidation beginning with the 5 carbon fatty acyl-CoA encountered in the last pass through the β-oxidation sequence?
• Where in the cell are Ketone bodies made, from which metabolite are they made, and how and where are ketone bodies used?
• Outline the oxidation steps that occur in omega ( ω ) oxidation.
• We have touched on saturated/unsaturated and even-/odd-numbered chain fatty acids, but dietary consumption also includes branched chain fatty acids. Locate and read the following article, and answer the questions below: Mukherji M, Schofield CJ, Wierzbicki AS, Jansen GA, Wanders RJA, and Lloyd M. (2003). Progress in Lipid Research, 42 (5): 359-376.
  • In which organelle not previously mentioned in this assignment does metabolism of some branched-chain fatty acids occur?
  • According to your text and this paper, what is the primary pathway for oxidation of long chain fatty acids in this
    organelle?
  • What name is given the oxidative pathway for branched-chain fatty acids?
  • What, in general terms, is an oxygenase?
  • In the proposed mechanism for 2-hydroxyphytanoyl-CoA lyase, what two products result from the attack of TPP on thioester?