Methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase [acylating], mitochondrial

ALDH6A1 encodes methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase (MMSDH), a mitochondrial enzyme that catalyzes the dehydrogenation of malonate and methylmalonate semialdehydes (UniProt: Q02252). This enzyme functions in the catabolism of valine, thymine, and beta-alanine-derived compounds, including uracil and cytidine, playing a role in amino acid and nucleotide base metabolism.

Mutations in ALDH6A1 cause methylmalonate semialdehyde dehydrogenase deficiency (MMSDHD, MIM 614105), a metabolic disorder marked by accumulation of beta-alanine and related organic acids in urine (UniProt: Q02252). The protein's mitochondrial localization reflects its involvement in metabolic homeostasis.

ALDH6A1 is associated with Alzheimer's Disease according to Chaparral curation. In post-mortem AD brain tissue, the protein is upregulated relative to age-matched controls, with a mean log2 fold-change of 0.62 across analyzed subcellular fractions (Chaparral AD proteomics). This elevation suggests altered metabolic enzyme abundance in AD pathology, though the functional consequences remain to be determined.