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  • Title: Ketoacidosis - Where Do the Protons Come From?
    Author: Green A, Bishop RE.
    Journal: Trends Biochem Sci; 2019 Jun; 44(6):484-489. PubMed ID: 30744927.
    Abstract:
    In extreme conditions ketosis can progress to ketoacidosis, a dangerous and potentially life-threatening condition. Ketoacidosis is most common in new or poorly treated type 1 diabetes. The acidosis is usually attributed to the 'acidic' nature of the ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone). However, acetoacetate and 3-hydroxybutyrate are produced not as acids but as their conjugate bases, and acetone is neither an acid nor a base. This raises the question of why severe ketosis is accompanied by acidosis. Here, we analyze steps in ketogenesis and identify four potential sources: adipocyte lipolysis, hydrolysis of inorganic pyrophosphate generated during synthesis of fatty acyl-coenzyme A (CoA), the reaction catalyzed by an enzyme in the β-oxidation pathway (3-hydroxyacyl-CoA dehydrogenase), and increased synthesis of CoA.
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