Question

Leucine and Valine are degraded by enzymes of the TCA cycle. Do the products of Leu and Val degradation contribute to triglyceride synthesis or to gluconeogenesis or both? Explain your answer with diagrams.

Answer 1

Ans. Yes, the products of Leu and Val degradation contribute to triglyceride synthesis and to gluconeogenesis. Leucine, isoleucine, and valine are (branched-chain amino acid and hence) essential amino acids that can be produced from their respective α-ketoacids.

Thus degradation or transamination of these amino acids will also produce respective α-keto acids. only one enzyme called transaminase or aminotransferase, may catalyze transamination of all three Leucine, isoleucine and valine. Transamination means the transfer of the α-amine group of an amino acid to a α-keto acid. Its a reversible reaction. In this the amino acid becomes a keto acid, and the α-keto acid which receive the amine group from amino acid is converted into the respective amino acid. Transamination of leucine, and valine (branched-chain amino acids) yields branched-chain α-keto acids.

The α-keto acids forms the during their oxidative decarboxylation. Acyl-CoA thioesters are further  converted into respective α,β-unsaturated acyl-CoA thioesters by α,β-dehydrogenation

The catabolism of leucine thus makes acetoacetate and acetyl-CoA via β-hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA) and the catabolism of valine forms succinyl-CoA which can enter into citric acid cycle.

Once the products are formed after deamination of amino acid, they enter into the the tricarboxylic acid (TCA) cycle (also known as the citric acid cycle or Krebs cycle) or the glycolytic pathway. Carbon skeletons of these products are also available for utilization in other biosynthetic pathways like glucose and fat biosynthetic/ anabolic pathways where glucose or fat are formed. Formation of either glucose or fat or both from the carbon skeleton of an amino acid depends on where it will enter into these two pathways. If amino acid carbon skeleton enter as acetyl-CoA, then only fat or ketone bodies can be produced and if carbon skeletons of other amino acids enter the pathways in other way so that glucose can be formed by gluconeogenesis.

Thus, leucine is ketogenic (produce ketone bodies) and valine are ketogenic and glucogenic. Ketone bodies produced from leucine are used to convert acetyl-CoA into long-chain fatty acids in brain. Valine, a glucogenic amino acid, is converted into glucose through gluconeogenesis.