Inborn errors of metabolism associated with 3-methylglutaconic aciduria.

ABSTRACT: A growing number of inborn errors of metabolism (IEM) associated with compromised mitochondrial energy metabolism manifest an unusual phenotypic feature: 3-methylglutaconic (3MGC) aciduria. Two major categories of 3MGC aciduria, primary and secondary, have been described. In primary 3MGC aciduria, IEMs in 3MGC CoA hydratase (AUH) or HMG CoA lyase block leucine catabolism, resulting in a buildup of pathway intermediates, including 3MGC CoA. Subsequent thioester hydrolysis yields 3MGC acid, which is excreted in urine. In secondary 3MGC aciduria, no deficiencies in leucine catabolism enzymes exist and 3MGC CoA is formed de novo from acetyl CoA. In the "acetyl CoA diversion pathway", when IEMs directly, or indirectly, interfere with TCA cycle activity, acetyl CoA accumulates in the matrix spac

SUBMITTER: Jones DE 

PROVIDER: S-EPMC8464523 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature