2. Fermentation of pyruvate to lactate would be slowed down. There would be a build up of pyruvate and more pyruvate getting converted to AcCoA and oxaloacetate, and entering the TCA cycle. In case there is low oxygen, the build up of pyruvate would be greater and production of ATP would stop altogether as oxidative phosphorylation is slowed, and NAD+ is not able to be regenerated via fermentation to maintain glycolysis.
1. TCA cycle would be slowed down and there would be more fermentation or generation of lactate. The enzyme that catalyzes conversion of pyruvate to acetyl-CoA is pyruvate dehydrogenase complex (PDC). Pyruvate enters the mitochondrial matrix via the mitochondrial pyruvate carrier (MPC) protein at the inner mitochondrial membrane (IMM) and mostly via voltage-dependent anion channels (VDAC) at the outer mitochondrial membrane (OMM).
2. When oxygen is abundant, fermentation is slowed down, but when high levels of lactate is generated from pyruvate, assuming this is in the skeletal muscle the lactate is transported to the liver and other organs that utilize lactate (eg., heart) through the blood stream. The lactate dehydrogenase (LDH) enzyme in these organs catalyzes the conversion of lactate to pyruvate. The pyruvate is oxidized into carbon dioxide generating ATP via the TCA cycle. In the liver, the pyruvate goes into creation of glucose via a process called gluconeogenesis (it's called the Cori Cycle).
1. Flux towards biomass production is increased via glycolysis. Reductive carboxylation is also increased with more alpha-ketoglutarate being converted to citrate. The citrate is shuttled to the cytosol to regenerate Acetyl-CoA for production of fatty acids and to increase biomass.
2. Glucose is mostly the only fuel for the human brain which needs a constant supply of it as it does not store fuel. During prolonged starvation, it could use ketone bodies generated by the liver as fuel. The skeletal muscle can use glucose, fatty acids and ketone bodies as major fuels and it also has a large store of glycogen. While actively contracting, the rate of glycolysis is greater than the TCA cycle. The lactate and alanine formed in the muscle is taken up by the liver and converted to glucose. In the resting muscle, fatty acids are the major fuel source.
1. Under both conditions of hypoxia and cancer, glycolytic flux is increased and flux of glucose through pyruvate dehydrogenase (PDH) into the TCA cycle is decreased, partially through activation of pyruvate dehydrogenase kinase (PDK). This could be happening to promote glucose uptake and anabolic metabolism i.e., increasing the concentration of central carbon metabolites available to drive biosynthesis.
2. The TCA cycle would slow down reducing oxidative phosphorylation and the total ATP production. It would also lower production of anabolic precursors to animo acids or acetyl-CoA/lipids via citrate and other TCA cycle intermediates.