Regulation of glycolysis

Regulation of glycolysis: Short-term regulation of glycolysis happens through:

• Allosteric activation or inhibition of enzymes
• Phosphorylation/dephosphorylation of enzymes

These short-term effects occur over minutes to hours.

Slower but more sustained regulation occurs through hormones that change how much enzyme is synthesized. These effects occur over hours to days.

Regular consumption of carbohydrate-rich meals, or administration of insulin, increases the levels of glucokinase, phosphofructokinase, and pyruvate kinase in the liver due to increased gene transcription. The opposite effects are seen in fasting/starvation.

Alternate fates of pyruvate:

1. Pyruvate to acetyl CoA by pyruvate dehydrogenase. Acetyl CoA can enter the TCA cycle or can be used for fatty acid synthesis.
2. Pyruvate to oxaloacetate by pyruvate carboxylase, requires biotin (vitamin B7); replenishes the TCA cycle and provides substrate for gluconeogenesis.

Energy yield from glycolysis:

1. Anaerobic glycolysis: 2 ATP are generated per molecule of glucose converted to 2 molecules of lactate. No net NADH production or consumption.
2. Aerobic glycolysis: Net gain of 2 ATP per glucose molecule and 2 NADH. Oxidation of NADH by ETC produces 3 ATP for each NADH. So, potential for a total of 2+3+3 = 8 ATP per glucose molecule. If you take into consideration metabolism of pyruvate also, which potentially can produce 2 NADH (6 ATP) plus 2 acetyl CoA (2 X 12 = 24 ATP), then the net ATP production is 8+6+24 = 38 ATP.

Oxidation of acetyl CoA generates ATP via oxidative phosphorylation as electrons flow from NADH and FADH2 to O2 (aka ETC). Acetyl CoA can be derived from amino acids, monosaccharides, and fatty acids and glycerol (both from fats). Glycolysis occurs in the cytosol.

Sites of metabolic reactions

Mitochondria: TCA cycle; fatty acid oxidation; pyruvate oxidation
Cytosol: glycolysis, HMP shunt, fatty acid synthesis, glycogen synthesis and breakdown
Nucleus: DNA and RNA synthesis
Lysosome: degradation of complex macromolecules
Gluconeogenesis is partly in cytoplasm and partly in mitochondria