Gluconeogenesis in the liver can utilize different precursors depending on what

Question

Gluconeogenesis in the liver can utilize different precursors depending on what is happening elsewhere the body. The liver can use lactate, which comes from the muscle during exertion and after exercise. It can also indirectly use alanine. a. What needs to happen in order for alanine to be used for gluconeogenesis? b. Under what conditions might alanine be the precursor for gluconeogenesis? The precursors to gluconcogenesis including acetyl Co-A and pyruvate can act as allosteric effectors to modulate the activity of PK, PEPCK, and pyruvate carboxylase. Describe the metabolic effects and the impact on a whole animal if the following mutations were present in the liver isoforms of the enzymes listed below. a. The allosteric binding site for alanine on pyruvate kinase is mutated, decreasing affinity for alanine. b. The regulatory phosphorylation site on pyruvate kinase is eliminated through a single amino acid mutation. c. The allosteric binding site for acetyl-CoA on pyruvate carboxylase is mutated, decreasing affinity for acetyl-CoA. d. The pyruvate carboxylase gene is mutated resulting in an enzyme that is catalytically inactive. e. The PEPCK gene is mutated resulting in an enzyme that is catalytically inactive.

Explanation / Answer

a. When pyruvate kinase is allosterically inhibited by alanine, it has decreased affinity for PEP as well. When there is mutation in alanine binding site, enzyme shows decreased affinity for alanine, in that case it will show high affinity for PEP. And the process of glycolysis will halt as there will be no allosteric inhibition of Pyruvate kinase.

b. It will adversely affect the enzyme and will reduce its binding affinity to PEP. But wont affect the binding affinity of ADP.

c. It will prevent the process of Biotin carboxylation and ATP dissociation , leading to reduced rate of reaction and decreased binding of substrates like HCO3-. All these factors will suspend the process of gluconeogenesis.

d. Mutation of Pyruvate carboxylase gene will stop the conversion of pyruvate to oxaloacetate, But It wont affect the total production of Oxaloacetate because Oxaloacetate can also be produced from other sources like krebs cycle from matlate.

e. It will stop the conversion of Oxaloacetate to PEP and there will be no gluconeogenesis at all.

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