MMADHC

This gene encodes a mitochondrial protein that is involved in an early step of vitamin B12 metabolism. Vitamin B12 (cobalamin) is essential for normal development and survival in humans. Mutations in this gene cause methylmalonic aciduria and homocystinuria type cblD (MMADHC), a disorder of cobalamin metabolism that is characterized by decreased levels of the coenzymes adenosylcobalamin and methylcobalamin. Pseudogenes have been identified on chromosomes 11 and X.

Full Name

METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, CBLD TYPE

Function

Involved in cobalamin metabolism and trafficking (PubMed:18385497, PubMed:23415655, PubMed:24722857, PubMed:26364851).

Plays a role in regulating the biosynthesis and the proportion of two coenzymes, methylcob(III)alamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl) (PubMed:18385497,PubMed:23415655, PubMed:24722857).

Promotes oxidation of cob(II)alamin bound to MMACHC (PubMed:26364851).

The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:27771510).

Biological Process

Cobalamin metabolic process Source: UniProtKB

Cellular Location

Mitochondrion
Cytoplasm

Involvement in disease

Methylmalonic aciduria and homocystinuria, cblD type (MAHCD):
An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include developmental delay, hyotonia, mental retardation, seizures, megaloblastic anemia. Some patients manifest combined methylmalonic aciduria and homocystinuria (referred to as cblD original), some have only isolated homocystinuria (cblD variant 1), and others have only methylmalonic aciduria (cblD variant 2).