Before discussing gluconeogenesis it is necessary to be clear on the following:
- What organism you are considering
- Under what physiological circumstances gluconeogenesis is occurring
- What is the substrate for gluconeogenesis
and, if one is considering mammals:
- Which tissue is performing the gluconeogenesis
- Which tissue(s) will consume the glucose produced
because these latter two are never the same,
or in other organisms:
- What is the glucose produced actually used for
Gluconeogenesis is performed almost exclusively by the liver, which is able to provide the NADH and ATP for this process from its oxidative metabolism. (The kidney also has a small capacity for gluconeogenesis, but the reason for this is another question). The tissues consuming the glucose are predominantly erythrocytes, brain and nervous tissue and muscle, depending on the circumstances.
Resting post-absorptive ‘lactate recycling’
Erythrocytes have no mitochondria so can only respire by anaerobic glycolysis, reducing the pyruvate to lactate (in order to regenerate NAD+). The lactate goes into the blood, and is taken up by the liver and oxidized to pyruvate. Gluconeogenesis converts the pyruvate to glucose which passes back into the bloodstream, restoring that used by the erythrocytes. (The brain also uses glucose here but I’ll deal with it below.)
‘Lactate recycling’ in exercise
Muscle has a certain aerobic capacity depending on type. However in vigorous exercise the skeletal muscle becomes anaerobic and obtains ATP for muscle contraction from aerobic glycolysis, again producing lactate. The liver glycolysis recycles this lactate to maintain the blood glucose, as in the previous section. (This overall co-ordination between tissues is often called ‘Cori Cycle’ in text books. However the name can be misleading, as it is not a chemical cycle like the tricarboxylic acid cycle or the urea cycle.)
In starvation the net supplies of energy will fall. However the one tissue that must be kept supplied with a glucose is the brain (even though it can obtain part of its energy requirements from other sources). Liver gluconeogenesis provides this, but substrates other than lactate are need to restore the glucose lost by net consumption after the liver glycogen reserves have been depleted. The main gluconeogenic precursors are a subset of amino acids from protein breakdown (the so-called glucogenic amino acids) which feed in at different parts of the pathway. Glycerol from the breakdown of triglycerides can also be used, but fatty acids themselves cannot, because they are converted to acetyl CoA, which condenses with oxaloacetate to feed into the tricarboxylic acid cycle, and produces no net carbon skeleton that could be used for glycolysis.
I am not a plant biochemist, so I am happy to be corrected if wrong, but I understand that gluconeogenesis is important after seed germination for production of hexoses for use in cell wall polysaccharides during growth. Seeds contain reserves of fat, which on germination is oxidized to acetyl CoA which passes into the tricarboxylic acid cycle. However plants (and some bacteria) are able to convert this to pyruvate by means of a pathway mammals lack — the glyoxylate cycle (http://www.ncbi.nlm.nih.gov/books/NBK22383/). So in plants the glucose produced is not being used to provide energy by oxidation, but as a biosynthetic precursor.
Gluconeogenesis is present in certain bacteria, where the pathway presumably arose (rather than in mammals). So it is of interest to consider its role there. Again, I am no bacteriologist, but the glyoxylate cycle is also present in bacteria, and it is likely that one function of gluconeogenesis would be to allow growth on fatty acids, with the glucose produced being required for synthesis of cell-wall polysaccharides.