MMACHC

Description

The MMACHC (metabolism of cobalamin associated C) is a protein-coding gene located on chromosome 1.

The MMACHC gene provides instructions for making a protein that helps convert vitamin B12 (also called cobalamin) into one of two molecules, adenosylcobalamin (AdoCbl) or methylcobalamin (MeCbl). AdoCbl is required for the normal function of an enzyme known as methylmalonyl CoA mutase. This enzyme helps break down certain protein building blocks (amino acids), fat building blocks (fatty acids), and cholesterol. AdoCbl is called a cofactor because it helps methylmalonyl CoA mutase carry out its function. MeCbl is also a cofactor, but for an enzyme known as methionine synthase. This enzyme converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.Research indicates that the MMACHC protein plays a role in processing different forms of vitamin B12 so that they can be converted to either of the cofactors, AdoCbl or MeCbl. MMACHC also interacts with another protein called MMADHC (produced from the MMADHC gene). Together these proteins transport the processed vitamin B12 to regions of the cell in which each cofactor is needed: specialized structures that serve as energy-producing centers (the mitochondria), where AdoCbl functions, or the fluid inside the cell (the cytoplasm), where MeCbl functions. Additional chemical reactions then convert vitamin B12 into AdoCbl or MeCbl.

The MMACHC gene encodes a protein that acts as a cytosolic chaperone for cobalamin (vitamin B12). It catalyzes the reductive decyanation of cyanocobalamin (CNCbl) to cob(II)alamin and cyanide, utilizing FAD or FMN as cofactors and NADPH as a cosubstrate. Cyanocobalamin is the inactive form of vitamin B12 obtained from the diet, and MMACHC converts it into the active cofactors methylcobalamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl). MMACHC forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, facilitating the transport of cobalamin across the lysosomal membrane into the cytosol. Within the cytosol, MMACHC participates in a multiprotein complex alongside MMADHC, MTRR, and MTR, ensuring the safe and efficient delivery of cobalamin to MTR for methionine production. Additionally, MMACHC functions as a glutathione transferase, catalyzing the dealkylation of MeCbl and AdoCbl to generate cob(I)alamin. This conversion is crucial for meeting cellular needs for both cofactors. MMACHC cannot utilize cysteine or homocysteine as substitutes for glutathione in this reaction.

MMACHC is also known as cblC.

Associated Diseases

Comprehensive carrier screening

Whole Exome Sequencing

Clinical Exome Sequencing