Gamma-butyrobetaine dioxygenase [SEP] found in taxon
and trimethylaminoacetone. Gamma-butyrobetaine dioxygenase also catalyses the oxidation of mildronate to form multiple products including malonic acid semialdehyde, dimethylamine, formaldehyde and (1-methylimidazolidin-4-yl)acetic acid, which is proposed to be formed via a Stevens rearrangement mechanism. Gamma-butyrobetaine dioxygenase is unique among other human 2OG oxygenases that it catalyses both hydroxylation (e.g  L-carnitine), demethylation (e.g  formaldehyde) and C-C bond formation (e.g  (1-methylimidazolidin-4-yl)acetic acid).
Inhibition.
Gamma-butyrobetaine dioxygenase is an inhibition target for 3-(2,2,2-trimethylhydraziniumyl)propionate
treatments of angina, stroke and chronic heart failure. However, there have been no randomized clinical trials to support the use of mildronate to treat any cardiovascular disease.
Mildronate has a similar structure to the natural substrate gamma-butyrobetaine, with a NH group replacing the CH of gamma-butyrobetaine at the C-4 position. A crystal structure of mldronate in complex with gamma-butyrobetaine dioxygenase was published, and it suggests mildronate bind to gamma-butyrobetaine dioxygenase in exactly the same way as gamma-butyrobetaine (PDB id: