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Trends Biochem Sci. 2019 Jun;44(6):484-489. doi: 10.1016/j.tibs.2019.01.005. Epub 2019 Feb 8.

Ketoacidosis - Where Do the Protons Come From?

Author information

1
Department of Chemistry and Biochemistry, SUNY Oneonta, 108 Ravine Parkway, Oneonta, NY 13820, USA. Electronic address: allan.green@oneonta.edu.
2
Department of Chemistry and Biochemistry, SUNY Oneonta, 108 Ravine Parkway, Oneonta, NY 13820, USA.

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.

PMID:
30744927
DOI:
10.1016/j.tibs.2019.01.005

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