Question

5.Consider the regulation of glycolysis, gluconeogenesis, pyruvate dehydrogenase, and the TCA cycle, how is the regulation of these pathways linked to thermodynamics? How are they linked to one another?

Answer 1

Gluconeogenesis and glycolysis are coordinated so that within a cell one pathway is relatively inactive while the other is highly active. If both sets of reactions were highly active at the same time, the net result would be the hydrolysis of four nucleotide triphosphates (two ATP plus two GTP) per reaction cycle. Both glycolysis and gluconeogenesis are highly exergonic under cellular conditions, and so there is no thermodynamic barrier to such simultaneous activity.

The basic idea of the TCA cycle consists in releasing the substrate carbon as CO2, while retaining the substrate hydrogen for “cold combustion” in the respiratory chain.

Alternate metabolic destinations of pyruvate

1. conversion to acetyl-CoA by PDH for complete degradation or for synthesis of fatty acids and cholesterol
2. carboxylation to oxaloacetate, for use in gluconeogenesis or in the citric acid cycle
3. synthesis of amino acids, e.g., transamination to alanine
4. reduction to lactate