MAE1 encodes the sole malic enzyme of Saccharomyces cerevisiae, a mitochondrial matrix enzyme that catalyses the oxidative decarboxylation of (S)-malate to pyruvate and CO2, reducing NAD+ or NADP+ (the yeast enzyme has been reported to use both). MAE1 is expressed constitutively, with a 3-4-fold induction during anaerobic growth on glucose. Mae1p provides an alternative route to pyruvate when pyruvate kinase is not available: pyk1 mae1 double mutants cannot grow on ethanol unless alanine or pyruvate is supplied, whereas mae1 single mutants lack a clear phenotype. Its role is therefore biosynthetic/anaplerotic (pyruvate for alanine, valine, leucine and isoleucine synthesis, and possibly intramitochondrial NADPH), rather than a step of the TCA cycle or of gluconeogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004470 malic enzyme activity | IDA PMID:9603875 Identification and characterization of MAE1, the Saccharomyc... | ACCEPT | Summary: IDA: Boles et al. showed that disruption of YKL029c/MAE1 abolished malic enzyme activity in extracts and that overexpression increased it up to 33-fold. The assay used NADP+, and the yeast enzyme has been reported to use both NAD+ and NADP+, so the cofactor-neutral parent term is appropriate. Core activity. Supporting Evidence: PMID:9603875 Disruption of open reading frame YKL029c, which is homologous to malic enzyme genes from other organisms, abolished malic enzyme activity in extracts of glucose-grown cells. PMID:9603875 malic enzyme from S. cerevisiae has been reported to use both NAD + and NADP + as electron acceptors |
| GO:0004470 malic enzyme activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (GO_REF:0000120) from ARBA and malic-enzyme InterPro signatures (IPR001891, IPR012301, IPR037062). Correct for Mae1p; redundant with IDA. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=(S)-malate + NAD(+) = pyruvate + CO2 + NADH; |
| GO:0004471 malate dehydrogenase (decarboxylating) (NAD+) activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001157969 seeded by S. pombe Mae2 (SPCC794.12c). Mae1p is a bona fide malic enzyme and the S. cerevisiae enzyme has been reported to use NAD+ as well as NADP+, so the NAD+-specific child term is acceptable, although cofactor preference in vivo has not been resolved for Mae1p. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=(S)-malate + NAD(+) = pyruvate + CO2 + NADH; PMID:9603875 malic enzyme from S. cerevisiae has been reported to use both NAD + and NADP + as electron acceptors |
| GO:0004471 malate dehydrogenase (decarboxylating) (NAD+) activity | IEA GO_REF:0000116 | ACCEPT | Summary: IEA from Rhea mapping (RHEA:12653, malate + NAD+ -> pyruvate + CO2 + NADH) of the UniProt catalytic activity, which UniProt infers by similarity to human ME2. Consistent with reported NAD+ use by the yeast enzyme. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=(S)-malate + NAD(+) = pyruvate + CO2 + NADH; PMID:9603875 malic enzyme from S. cerevisiae has been reported to use both NAD + and NADP + as electron acceptors |
| GO:0004471 malate dehydrogenase (decarboxylating) (NAD+) activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from human mitochondrial NAD(P)-malic enzyme ME2 (P23368). Mae1p is a mitochondrial malic enzyme homolog; transfer of NAD+-dependent oxidative decarboxylation is reasonable and consistent with the yeast enzyme using NAD+ and NADP+. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=(S)-malate + NAD(+) = pyruvate + CO2 + NADH; PMID:9603875 malic enzyme from S. cerevisiae has been reported to use both NAD + and NADP + as electron acceptors |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: HDA: Mae1p identified in the purified mitochondrial proteome. Consistent with fractionation data. Supporting Evidence: PMID:14576278 From >20 million MS spectra, 750 different proteins were identified |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: HDA: Mae1p identified in the PROMITO mitochondrial proteome. Consistent with fractionation data. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: HDA: Mae1p detected in quantitative mitochondrial proteomics across carbon sources. Consistent. Supporting Evidence: PMID:24769239 Label free quantitative analysis of protein accumulation revealed significant variation of 176 mitochondrial proteins |
| GO:0005739 mitochondrion | IDA PMID:9603875 Identification and characterization of MAE1, the Saccharomyc... | ACCEPT | Summary: IDA: subcellular fractionation showed latent, particulate malic enzyme activity; Mae1p also carries a predicted mitochondrial presequence. Core location (matrix is more specific). Supporting Evidence: PMID:9603875 Subcellular fractionation experiments indicated that malic enzyme in S. cerevisiae is a mitochondrial enzyme. |
| GO:0005739 mitochondrion | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (gluconeogenesis I, GLUCONEO-PWY-1) placing the malic enzyme step in mitochondria; the location itself is correct. Supporting Evidence: PMID:9603875 Subcellular fractionation experiments indicated that malic enzyme in S. cerevisiae is a mitochondrial enzyme. |
| GO:0005739 mitochondrion | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (TCA cycle, TCA-EUK-PWY) placing the malic enzyme step in mitochondria; location correct even though Mae1p is not a TCA-cycle enzyme. Supporting Evidence: PMID:9603875 Subcellular fractionation experiments indicated that malic enzyme in S. cerevisiae is a mitochondrial enzyme. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0170 Mitochondrion matrix), based on fractionation and proteomics. Most specific supported location; core. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA from the superpathway of TCA cycle and glyoxylate cycle (PWY3O-94), which places the malic enzyme reaction in the cytosol. Mae1p is the only malic enzyme of S. cerevisiae and is mitochondrial by fractionation, presequence and proteomics; no cytosolic pool has been reported. This is a superpathway compartment artefact. Reason: Contradicted by experimental localisation of Mae1p to mitochondria. Supporting Evidence: PMID:9603875 Subcellular fractionation experiments indicated that malic enzyme in S. cerevisiae is a mitochondrial enzyme. |
| GO:0006094 gluconeogenesis | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA from gluconeogenesis I (GLUCONEO-PWY-1), which includes malate -> pyruvate by malic enzyme (a MetaCyc route for C4-acid utilisation). In S. cerevisiae Mae1p runs in the opposite direction to gluconeogenic flux from C2 substrates (it makes pyruvate from malate); its demonstrated role on ethanol is to provide pyruvate for biosynthesis (alanine/branched-chain amino acids), not to make PEP or sugars. mae1 single mutants have no clear phenotype on gluconeogenic carbon sources. Reason: Pathway-inherited assignment not supported by the physiology of Mae1p in yeast. Supporting Evidence: PMID:9603875 Mutants lacking both enzymes could be rescued by addition of alanine or pyruvate to ethanol cultures. PMID:9603875 the mitochondrial malic enzyme can meet the biosynthetic requirement of S. cerevisiae for pyruvate during growth on ethanol or acetate |
| GO:0006520 amino acid metabolic process | IMP PMID:9603875 Identification and characterization of MAE1, the Saccharomyc... | ACCEPT | Summary: IMP: pyk1 mae1 double mutants cannot grow on ethanol unless alanine or pyruvate is supplied, showing that Mae1p provides pyruvate as a precursor for amino acid biosynthesis. A broad term but consistent with the data; the more precise description is pyruvate biosynthesis for amino-acid synthesis. Supporting Evidence: PMID:9603875 Mutants lacking both enzymes could be rescued by addition of alanine or pyruvate to ethanol cultures. PMID:9603875 pyruvate still has to be generated for amino acid biosynthesis |
| GO:0008948 oxaloacetate decarboxylase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: IEA from Rhea mapping (RHEA:15641) of the UniProt by-similarity annotation that malic enzymes also decarboxylate oxaloacetate. This is a known secondary activity of malic enzymes (ME2), but it has not been measured for Mae1p and is not its physiological role. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=oxaloacetate + H(+) = pyruvate + CO2; |
| GO:0008948 oxaloacetate decarboxylase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from human ME2 (P23368), which has oxaloacetate decarboxylase side activity. Plausible but untested for Mae1p; non-core. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=oxaloacetate + H(+) = pyruvate + CO2; |
| GO:0008948 oxaloacetate decarboxylase activity | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA from gluconeogenesis I attaching an oxaloacetate decarboxylase reaction to Mae1p. Malic enzymes generally have this side activity, but there is no yeast evidence that Mae1p decarboxylates oxaloacetate in vivo, and the gluconeogenesis context is itself not supported for Mae1p. Kept as non-core, consistent with the IEA/ISS rows. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=oxaloacetate + H(+) = pyruvate + CO2; |
| GO:0009060 aerobic respiration | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA from TCA cycle, aerobic respiration (TCA-EUK-PWY). Mae1p is not a TCA-cycle enzyme; it is a mitochondrial anaplerotic/biosynthetic enzyme whose expression is constitutive and slightly induced anaerobically, and mae1 nulls have no respiratory phenotype. Reason: Superpathway inheritance; Mae1p does not catalyse a step of aerobic respiration. Supporting Evidence: PMID:9603875 Growth studies with mutants demonstrated that presence of either Pyk1p or Mae1p is required for growth on ethanol. |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000002 | MODIFY | Summary: IEA from InterPro2GO malic-enzyme signatures mapping to the generic oxidoreductase (CH-OH donor, NAD/NADP acceptor) class. Correct but uninformative; malic enzyme activity is more precise. Proposed replacements: malic enzyme activity Supporting Evidence: PMID:9603875 Disruption of open reading frame YKL029c, which is homologous to malic enzyme genes from other organisms, abolished malic enzyme activity in extracts of glucose-grown cells. |
| GO:0030060 L-malate dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (gluconeogenesis I) assigning L-malate dehydrogenase (NAD+) activity (malate -> oxaloacetate, EC 1.1.1.37) to Mae1p. Mae1p is a decarboxylating malic enzyme (EC 1.1.1.38/40) producing pyruvate + CO2; it does not form oxaloacetate. The non-decarboxylating MDH reaction is carried out by MDH1/2/3, whose triple deletion abolishes cellular MDH activity. Reason: Wrong EC/reaction attached to Mae1p by the pathway conversion. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=(S)-malate + NAD(+) = pyruvate + CO2 + NADH; PMID:1447211 Combined disruption of MDH1, MDH2, and MDH3 loci in a haploid strain resulted in the absence of detectable cellular malate dehydrogenase activity. |
| GO:0030060 L-malate dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA from the TCA/glyoxylate superpathway (PWY3O-94) assigning malate dehydrogenase (EC 1.1.1.37) to Mae1p. Same error: Mae1p is a decarboxylating malic enzyme, not a malate dehydrogenase. Reason: Wrong reaction for this enzyme. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=(S)-malate + NAD(+) = pyruvate + CO2 + NADH; |
| GO:0030060 L-malate dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA from TCA cycle (TCA-EUK-PWY) assigning malate dehydrogenase (EC 1.1.1.37) to Mae1p. Same error; the TCA-cycle MDH step is catalysed by Mdh1p. Reason: Wrong reaction for this enzyme. Supporting Evidence: file:yeast/MAE1/MAE1-uniprot.txt Reaction=(S)-malate + NAD(+) = pyruvate + CO2 + NADH; |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: IEA from InterPro IPR012302 (malic enzyme NAD-binding domain). Mae1p uses NAD(P)+ as cofactor, so the binding is real, but it is part of the catalytic activity rather than a separate function. Supporting Evidence: PMID:9603875 malic enzyme from S. cerevisiae has been reported to use both NAD + and NADP + as electron acceptors |
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Experiment: Purify recombinant Mae1p and determine kinetic constants with NAD+ and NADP+, and test oxaloacetate decarboxylase side activity; combine with mitochondrial NADPH sensors in mae1 vs wild type under anaerobiosis.
Mitochondrial malic enzyme; catalyzes the oxidative decarboxylation of malate to pyruvate, which is a key intermediate in sugar metabolism and a precursor for synthesis of several amino acids
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