This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: malate/L-aspartate shuttle pathway
|Superclasses:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Proteinogenic Amino Acids Degradation → L-aspartate Degradation|
In this eukaryotic route of aspartate degradation, aspartate is converted to malate as part of the reversible malate-aspartate shuttle. This pathway spans the mitochondrial and cytoplasmic spaces, transferring reducing equivalents across the mitochondrial membrane. It is one of several shuttle mechanisms used to transfer electrons from cytosolic NADH produced by glycolysis into the mitochondrion, because NADH itself cannot cross the inner mitochondrial membrane. Inside the mitochondrion, NADH can be oxidized by the electron transport chain to produce ATP.
In the cytosolic reactions of this shuttle shown here, oxaloacetate produced by transamination of aspartate is reduced to malate by electrons from NADH. Malate is transported into the mitochondrial matrix via the malate-α-ketoglutarate carrier. There, malate is oxidized by NAD+ back to oxaloacetate, forming NADH. Mitochondrial oxaloacetate (which also does not readily cross the inner mitochondrial membrane) is transaminated to aspartate, which can be transported back to the cytosol via the glutamate-aspartate carrier. In the cytosol, oxaloacetate is regenerated by transamination of aspartate. Because this shuttle is reversible, electrons from NADH are brought into the mitochondrion when the NADH/NAD+ ratio is higher in the cytosol than in the mitochondrial matrix. The malate-aspartate shuttle yields approximately 3 molecules of ATP per molecule of cytosolic NADH [Voet04].
In mammals, this shuttle is found in liver, heart and kidney. The malate-aspartate shuttle may be present in fungi [Cavero03]. In plants, however, a malate/oxaloacetate shuttle has been described [Pastore03].
In another route of aspartate degradation in eukaryotes and prokaryotes, aspartate is converted to the corresponding keto acid, oxaloacetate (a TCA cycle I (prokaryotic) intermediate), by the transamination reaction shown here (see pathway L-aspartate degradation I). This reversible reaction also biosynthesizes aspartate (see pathway L-aspartate biosynthesis). In addition, aspartate is a precursor for many other compounds including lysine, threonine, methionine and NAD+ (see aspartate superpathway and pathway L-aspartate biosynthesis). In mammals and most land vertebrates, aspartate can also be degraded by entering the urea cycle at the point of citrulline, and is ultimately converted to fumarate (see pathway urea cycle). In prokaryotes, aspartate can be degraded to fumarate by aspartate ammonia-lyase (see pathway L-glutamate degradation II).
Variants: L-aspartate degradation I
Cavero03: Cavero S, Vozza A, del Arco A, Palmieri L, Villa A, Blanco E, Runswick MJ, Walker JE, Cerdan S, Palmieri F, Satrustegui J (2003). "Identification and metabolic role of the mitochondrial aspartate-glutamate transporter in Saccharomyces cerevisiae." Mol Microbiol 50(4);1257-69. PMID: 14622413
Pastore03: Pastore D, Di Pede S, Passarella S (2003). "Isolated durum wheat and potato cell mitochondria oxidize externally added NADH mostly via the malate/oxaloacetate shuttle with a rate that depends on the carrier-mediated transport." Plant Physiol 133(4);2029-39. PMID: 14671011
Allen64: Allen, S.H., Kellermeyer, R.W., Ssjernholm, R.L., Wood, H.G. (1964). "Purification and properties of enzymes involved in the propionic acid fermentation." J Bacteriol 87;171-87. PMID: 14102852
Beh93: Beh M, Strauss G, Huber R, Stetter K-O, Fuchs G (1993). "Enzymes of the reductive citric acid cycle in the autotrophic eubacterium Aquifex pyrophilus and in the archaebacterium Thermoproteus neutrophilus." Arch Microbiol 160: 306-311.
Berkemeyer98: Berkemeyer M, Scheibe R, Ocheretina O (1998). "A novel, non-redox-regulated NAD-dependent malate dehydrogenase from chloroplasts of Arabidopsis thaliana L." J Biol Chem 273(43);27927-33. PMID: 9774405
Birolo00: Birolo L, Tutino ML, Fontanella B, Gerday C, Mainolfi K, Pascarella S, Sannia G, Vinci F, Marino G (2000). "Aspartate aminotransferase from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC 125. Cloning, expression, properties, and molecular modelling." Eur J Biochem 267(9);2790-802. PMID: 10785402
BousquetLemerci90: Bousquet-Lemercier B, Pol S, Pave-Preux M, Hanoune J, Barouki R (1990). "Properties of human liver cytosolic aspartate aminotransferase mRNAs generated by alternative polyadenylation site selection." Biochemistry 29(22);5293-9. PMID: 1974457
Crow83: Crow KE, Braggins TJ, Hardman MJ (1983). "Human liver cytosolic malate dehydrogenase: purification, kinetic properties, and role in ethanol metabolism." Arch Biochem Biophys 225(2);621-9. PMID: 6625603
DAniello05a: D'Aniello A, Fisher G, Migliaccio N, Cammisa G, D'Aniello E, Spinelli P (2005). "Amino acids and transaminases activity in ventricular CSF and in brain of normal and Alzheimer patients." Neurosci Lett 388(1);49-53. PMID: 16039064
Felbeck80: Felbeck H, Grieshaber MK (1980). "Investigations on some enzymes involved in the anaerobic metabolism of amino acids of Arenicola marina L." Comparative Biochemistry and Physiology Part B: Comparative Biochemistry 66(2);205-213.
Fields06: Fields PA, Rudomin EL, Somero GN (2006). "Temperature sensitivities of cytosolic malate dehydrogenases from native and invasive species of marine mussels (genus Mytilus): sequence-function linkages and correlations with biogeographic distribution." J Exp Biol 209(Pt 4);656-67. PMID: 16449560
Fotheringham86: Fotheringham IG, Dacey SA, Taylor PP, Smith TJ, Hunter MG, Finlay ME, Primrose SB, Parker DM, Edwards RM (1986). "The cloning and sequence analysis of the aspC and tyrB genes from Escherichia coli K12. Comparison of the primary structures of the aspartate aminotransferase and aromatic aminotransferase of E. coli with those of the pig aspartate aminotransferase isoenzymes." Biochem J 1986;234(3);593-604. PMID: 3521591
Kim99: Kim SY, Hwang KY, Kim SH, Sung HC, Han YS, Cho Y (1999). "Structural basis for cold adaptation. Sequence, biochemical properties, and crystal structure of malate dehydrogenase from a psychrophile Aquaspirillium arcticum." J Biol Chem 274(17);11761-7. PMID: 10206992
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