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LDH is present in all human tissues. In some, the reaction as given below goes p

ID: 171710 • Letter: L

Question

LDH is present in all human tissues. In some, the reaction as given below goes predominantly from left to right, in others mainly from right to left. Explain in which direction would you expect to predominate in a) vigorously contracting skeletal muscle, b) the extremely well-oxygenated cells of cardiac muscle? Look at the reactions occurring in the glycolytic pathway; identify specifically why the conversion of pyruvate to lactate is necessary for the production of ATP to continue, when the Krebs Cycle and electron transport pathways are down-regulated during periods of high ATP demand.

pyruvate + reduced cofactor <- -> lactate + oxidised cofactor

Explanation / Answer

(a) In vigorously contracting skeletal muscle goes predominantly from left to right.

(b) In the extremely well-oxygenated cells of cardiac muscle goes predominantly from right to left.

Pyruvate, the first designated substrate of the gluconeogenic pathway, can then be used to generate glucose. All citric acid cycle intermediates, through conversion to oxaloacetate, amino acids other than lysine or leucine, and glycerol can also function as substrates for gluconeogenesis. Transamination or deamination of amino acids facilitates entering of their carbon skeleton into the cycle directly (as pyruvate or oxaloacetate), or indirectly via the citric acid cycle. Whether fatty acids can be converted into glucose in animals has been a longstanding question in biochemistry. It is known that odd-chain fatty acids can be oxidized to yield propanol CoA, a precursor for succinyl CoA, which can be converted to pyruvate and enter into gluconeogenesis.

Gluconeogenesis is a pathway consisting of eleven enzyme-catalyzed reactions. The pathway can begin in the mitochondria or cytoplasm, depending on the substrate being used. Many of the reactions are the reversible steps found in glycolysis.

Gluconeogenesis begins in the mitochondria with the formation of oxaloacetate through carboxylation of pyruvate. This reaction also requires one molecule of ATP, and is catalysed by pyruvate carboxylase. This enzyme is stimulated by high levels of acetyl -CoA (produced in -oxidation in the liver) and inhibited by high levels of ADP.