I understand that when there is a shortage of oxygen cells convert the pyruvic acid from glycolysis to lactic acid to regenerate NAD+. What I don’t understand is how they switch to anaerobic metabolism occurs. Is there a certain chemical message that triggers this?

  • $\begingroup$ Are you referring to human cells? $\endgroup$
    – Cell
    May 8 '19 at 17:35
  • $\begingroup$ Yes, the respiration in human being cells. $\endgroup$
    – kgemp
    May 8 '19 at 19:05

The simplest method of control of metabolism is by substrate concentration. So if the concentration of NADH and pyruvate is low, lactate dehydrogenase cannot function. When they build up it can and will.

lactate dehydrogenase reaction

The situation is more complicated than this, because pyruvate will only build up if it is not converted to acetyl CoA by the pyruvate dehydrogenase complex (see Berg et al. section 17.1.1):

pyruvate dehydrogenase reaction

Although the overall reaction is oxidative, and ultimately requires NAD+, the latter is not directly involved in the initial irreversible reaction. It is presumably for this reason that the reaction is also controlled, either allosterically (in bacteria) or by phosphorylation (in mammals). In either case the regulators are the small molecules the concentration of which is altered by the lack of oxygen: NAD+/NADH and ATP/ADP. The figure below and its legend is also from Berg et al. (section 17.2.1) — available through NCBI Bookshelf.

enter image description here

[The complex is inhibited by its immediate products, NADH and acetyl CoA. The pyruvate dehydrogenase component is also regulated by covalent modification. A specific kinase phosphorylates and inactivates pyruvate dehydrogenase, and a phosphatase actives the dehydrogenase by removing the phosphoryl (group). The kinase and the phosphatase also are highly regulated enzymes.]

The actual situation is quite complex and this is something of a simplification.

  • $\begingroup$ Thanks, can you give me the link so i could read more about the over all change that will make lactate dehydrogenase function? $\endgroup$
    – kgemp
    May 8 '19 at 19:10
  • $\begingroup$ @kgemp Done. You can only search (not browse) books on the NCBI bookshelf, but the two links I have given should provide a reasonable starting point. $\endgroup$
    – David
    May 8 '19 at 22:18

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