In enzymology, a malate dehydrogenase (oxaloacetate-decarboxylating) (EC 1.1.1.38) , also termed as malic enzyme 2 (ME2), is an enzyme that catalyzes the chemical reaction below
| malate dehydrogenase (oxaloacetate-decarboxylating) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 malic enzyme tetramer, Human | |||||||||
| Identifiers | |||||||||
| EC no. | 1.1.1.38 | ||||||||
| CAS no. | 9080-52-8 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
- (S)-malate + NAD+ pyruvate + CO2 + NADH
Thus, the two substrates of this enzyme are (S)-malate and NAD+, whereas its 3 products are pyruvate, CO2, and NADH.
This enzyme (ME2) belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is (S)-malate:NAD+ oxidoreductase (oxaloacetate-decarboxylating). Other names in common use include malic enzyme, pyruvic-malic carboxylase, NAD+-specific malic enzyme, NAD+-malic enzyme, and NAD+-linked malic enzyme. This enzyme participates in pyruvate metabolism.
Biological function edit
Malic enzyme 2 participates in pyruvate metabolism and carbon fixation in plants. In mammals, ME2 is allosterically activated by fumarate, which is distinctive from the other two malic enzymes (ME1 and ME3). The Krebs cycle intermediate fumarate links metabolism to mitobiogenesis through binding to malic enzyme 2 (ME2). Mechanistically, fumarate binds ME2 with two complementary consequences. First, promoting the formation of ME2 dimers, which activate deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT). DUT fosters thymidine generation and an increase of mtDNA. Second, fumarate-induced ME2 dimers abrogate ME2 monomer binding to mitochondrial ribosome protein L45, freeing it for mitoribosome assembly and mtDNA-encoded protein production. Methylation of the ME2-fumarate binding site by protein arginine methyltransferase-1 inhibits fumarate signaling to constrain mitobiogenesis. Notably, acute myeloid leukemia is highly dependent on mitochondrial function and is sensitive to targeting of the fumarate-ME2 axis.[1]
Structural studies edit
As of late 2007, 6 structures have been solved for this class of enzymes, with PDB accession codes 1DO8, 1EFK, 1EFL, 1GZ3, 1LLQ, 1O0S, 1PJ2, 1PJ3, 1PJ4, 1PJL, 1QR6, 1WW8, and 2DVM.
See also edit
References edit
- ^ Wang YP, Sharda A, Xu SN, van Gastel N, Man CH, Choi U, Leong WZ, Li X, Scadden DT (May 2021). "Malic enzyme 2 connects the Krebs cycle intermediate fumarate to mitochondrial biogenesis". Cell Metabolism. 33 (5): 1027–1041. doi:10.1016/j.cmet.2021.03.003. PMC 10472834. PMID 33770508.
