Reactome | MDH1 reduces OA

MDH1 reduces OA

Stable Identifier

R-HSA-9856871

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Cytosolic MDH1 (malate dehydrogenase 1) catalyzes the reversible reaction of oxaloacetate (OA) and NADH + H+ to form malate (MAL) and NAD+ (Friedrich et al. 1988; Lo et al. 2005). This reaction provides the malate-aspartate shuttle with reducing equivalents that are transported in the form of MAL into the mitochondrion, and are available there as NADH from the reverse reaction catalyzed by MDH2. Sources of cytosolic NADH are glycolysis, serine biosynthesis, and peroxisomal fatty acid oxidation (reviewed by Borst, 2020). The dimeric structure of the human dehydrogenase is inferred from human and pig crystallographic data (McCue & Finzel, 2021; Birktoft et al. 1989). Mutations in MDH1 can cause a form of early-onset epileptic encephalopathy (DEE88, MIM:618959; Broeks et al., 2019).

Literature References

PubMed ID	Title	Journal	Year
3052244	Biochemical and genetic identity of alpha-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes Friedrich, CA, Ferrell, RE, Siciliano, MJ, Kitto, GB	Ann Hum Genet	1988
22971926	Cytosolic malate dehydrogenase regulates senescence in human fibroblasts Lee, SM, Dho, SH, Ju, SK, Maeng, JS, Kim, JY, Kwon, KS	Biogerontology	2012
2775751	Refined crystal structure of cytoplasmic malate dehydrogenase at 2.5-A resolution Birktoft, JJ, Rhodes, G, Banaszak, LJ	Biochemistry	1989
32916028	The malate-aspartate shuttle (Borst cycle): How it started and developed into a major metabolic pathway Borst, P	IUBMB Life	2020
31538237	MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy Broeks, MH, Shamseldin, HE, Alhashem, A, Hashem, M, Abdulwahab, F, Alshedi, T, Alobaid, I, Zwartkruis, F, Westland, D, Fuchs, S, Verhoeven-Duif, NM, Jans, JJM, Alkuraya, FS	Hum Genet	2019
15565635	Developmental regulation and cellular distribution of human cytosolic malate dehydrogenase (MDH1) Lo, AS-Y, Liew, C-T, Ngai, S-M, Tsui, SK-W, Fung, K-P, Lee, C-Y, Waye, MM-Y	J Cell Biochem	2005
35036692	Structural Characterization of the Human Cytosolic Malate Dehydrogenase I McCue, WM, Finzel, BC	ACS Omega	2022