Choline dehydrogenase (CHDH) (CHDH)

Choline dehydrogenase (CHDH) is a mitochondrial matrix enzyme that catalyzes the first step of choline catabolism, converting choline into betaine aldehyde using FAD as a cofactor (UniProt Q8NE62). This process is the rate-limiting step in the synthesis of betaine, an essential osmolyte and methyl donor for the remethylation of homocysteine to methionine (PMID: 11481232). In clinical contexts, the choline oxidation pathway is significant because its intermediates are linked to the production of trimethylamine N-oxide (TMAO), a pro-atherogenic metabolite associated with increased risks of cardiovascular disease and chronic kidney disease (PMID: 25591118, PMID: 28435104). Research into CHDH inhibitors aims to reduce TMAO levels and mitigate metabolic syndrome, although no specific drugs are currently FDA-approved for this indication. Because choline is also a precursor for the neurotransmitter acetylcholine and the phospholipid phosphatidylcholine, therapeutic modulation of CHDH must be carefully managed to avoid systemic choline deficiency or neurological side effects (PMID: 15505130). Additionally, genetic polymorphisms in CHDH have been linked to non-alcoholic fatty liver disease and altered sperm function (PMID: 30643115).

Other names

Choline oxidaseCholine:acceptor oxidoreductaseCholine oxidation enzymesCholine oxidation pathway enzymes

Competitive inhibition of the choline binding site on the enzyme, preventing the oxidation of choline to betaine aldehyde and subsequently reducing the formation of trimethylamine (TMA) precursors and betaine.