4.3.2.1: argininosuccinate lyase
This is an abbreviated version!
For detailed information about argininosuccinate lyase, go to the full flat file.
Word Map on EC 4.3.2.1
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4.3.2.1
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ornithine
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arginase
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citrulline
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transcarbamylase
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ammonia
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aciduria
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l-arginine
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hyperammonemia
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duck
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delta-crystallins
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carbamyl
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lenses
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carbamoyltransferase
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carbamoylphosphate
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citrullinemia
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urea-cycle
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n-acetylglutamate
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ureotelic
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medicine
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ureogenesis
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6.3.4.5
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reptilian
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pharmacology
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drug development
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diagnostics
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analysis
- 4.3.2.1
- ornithine
- arginase
- citrulline
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transcarbamylase
- ammonia
- aciduria
- l-arginine
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hyperammonemia
- duck
-
delta-crystallins
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carbamyl
- lenses
-
carbamoyltransferase
- carbamoylphosphate
- citrullinemia
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urea-cycle
- n-acetylglutamate
-
ureotelic
- medicine
-
ureogenesis
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6.3.4.5
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reptilian
- pharmacology
- drug development
- diagnostics
- analysis
Reaction
Synonyms
AL, ARG4, ArgH, arginine-succinate lyase, argininosuccinase, Argininosuccinate lyase, argininosuccinic acid lyase, Arginosuccinase, ASAL, ASL, delta2 crystallin, delta2-crystallin, hASL, L-argininosuccinate arginine-lyase, lyase, argininosuccinate, Rv1659
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General Information
General Information on EC 4.3.2.1 - argininosuccinate lyase
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malfunction
metabolism
physiological function
additional information
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a point mutation of a gene encoding argininosuccinate lyase causes a short root phenotype in the root elongation defect 1 mutant ref1, the enzyme activity is lost by the mutation R140L in OsASL1.1. The mutant has a shorter length from the quiescent center to the starting point of the elongation zone but a similar cell size and number of lateral and crown roots, and similar radial structure and nutrient uptake patterns compared to the wild-type. The mutant phenotype can be rescued by exogenous addition of arginine, but not by other amino acids
malfunction
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an increase in aspartate- and citrulline-derived argininosuccinate is a consequence of enzyme inhibition by high levels of fumarate in fumarate hydratase-deficient cells. In these cells, argininosuccinate is not produced from citrulline and aspartate in FH-deficient cells but rather from arginine and fumarate
malfunction
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argininosuccinate aciduria is observed in patients deficient in the enzyme. An increase in aspartate- and citrulline-derived argininosuccinate is a consequence of enzyme inhibition by high levels of fumarate in fumarate hydratase-deficient cells. In these cells, argininosuccinate is not produced from citrulline and aspartate in FH-deficient cells but rather from arginine and fumarate
malfunction
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argininosuccinic aciduria, ASA, MIM 207900, is the second most common human urea cycle disorder and is caused by deficiency of argininosuccinate lyase. Subjects with ASA disease cannot generate arginine from citrulline. Loss of the enzyme also leads to reduced NO synthesis due to decreased endogenous arginine synthesis as well as reduced utilization of extracellular arginine for NO production in humans
malfunction
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loss of enterocyte-derived enzyme results in increased incidence of necrotizing enterocolitis, phenotype, overview
malfunction
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loss of enterocyte-derived enzyme results in increased incidence of necrotizing enterocolitis, phenotype, overview
malfunction
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loss of the enzyme leads to reduced NO synthesis due to decreased endogenous arginine synthesis as well as reduced utilization of extracellular arginine for NO production in mice. Enzyme hypomorphic mice show global NO deficiency and evidence of multi-organ dysfunction, phenotypes, hypomorphic mouse model of enzyme deficiency, overview
malfunction
argininosuccinate lyase deficiency (ASLD) is a rare autosomal-recessive urea cycle defect caused by mutations in the ASL gene encoding argininosuccinate lyase. ASLD has a broad clinical spectrum ranging from life-threatening severe neonatal to asymptomatic forms. Different levels of residual ASL activity probably contribute to the phenotypic variability. All ASL mutations that are identified in patients with late onset or mild clinical and biochemical courses by ASL expression in human embryonic kidney are investigated
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ASL synthesizes the second step in production of arginine, which is a part of the congenital urea cycle
metabolism
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biological activity in liver, ileum, small intestine, heart, lung and kidney within the urea and nitric oxide cycle
metabolism
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synthesizes the second last step in the conversion of ammonia into urea
metabolism
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small heat shock protein, alphaA-crystallin, functions as a molecular chaperone, and enhances thermal stability of both delta-crystallin and ASL. Thermal unfolding of delta-crystallin or ASL in the presence of alphaA-crystallin follows a similar three-state model. A stable intermediate which retains about 30% alpha-helical structure is observed. Protection from thermal denaturation by alphaA-crystallin is by interaction with partly unfolded ASL to form high molecular weight heteroligomers. Aggregate formation of ASL is significantly reduced in the presence of alphaA-crystallin. The extent of protection of ASL at different ratios of alpahA-crystallin is described by hyperbolic curves, suggesting the preferential recognition of partly unfolded ASL by alphaA-crystallin
metabolism
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Sulfolobus solfataricus lacks ornithine acetyltransferase and thus forms N-acetylglutamate exclusively via the energetically less favourable reaction catalysed by N-acetylglutamate synthase, investing 1 mol of acetyl CoA per mol of N-acetyl intermediate synthesized
metabolism
last enzyme in the arginine biosynthesis pathway
metabolism
as part of the urea cycle, the enzyme is essential for ammonia detoxification and L-arginine synthesis
metabolism
last enzyme of the arginine biosynthesis pathway. Esential enzyme for the growth and survival of Mycobacterium tuberculosis
metabolism
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Sulfolobus solfataricus lacks ornithine acetyltransferase and thus forms N-acetylglutamate exclusively via the energetically less favourable reaction catalysed by N-acetylglutamate synthase, investing 1 mol of acetyl CoA per mol of N-acetyl intermediate synthesized
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metabolism
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last enzyme of the arginine biosynthesis pathway. Esential enzyme for the growth and survival of Mycobacterium tuberculosis
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argininosuccinate lyase in enterocytes protects from development of necrotizing enterocolitis, cell-autonomous role of the enzyme. The enzyme is required to maintain a NO synthesis complex containing NO synthase, argininosuccinate synthase, HSP90, and the arginine transporter SLC7A1
physiological function
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argininosuccinate lyase in enterocytes protects from development of necrotizing enterocolitis, cell-autonomous role of the enzyme. The enzyme is required to maintain a NO synthesis complex containing NO synthase, argininosuccinate synthase, HSP90, and the arginine transporter SLC7A1
physiological function
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loss of function of fumarate hydratase, the mitochondrial tumor suppressor and tricarboxylic acid cycle enzyme, is associated with a highly malignant form of papillary and collecting duct renal cell cancer. The accumulation of fumarate leads to reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells from Fh1-deficient humans, making these cells auxotrophic for arginine, which opens a therapeutic perspective for the cure of hereditary leiomyomatosis and renal cell cancer. The urea cycle metabolite argininosuccinate is a common metabolic biomarker of FH deficiency
physiological function
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loss of function of fumarate hydratase, the mitochondrial tumor suppressor and tricarboxylic acid cycle enzyme, is associated with a highly malignant form of papillary and collecting duct renal cell cancer. The accumulation of fumarate leads to reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells from Fh1-deficient mice, making these cells auxotrophic for arginine
physiological function
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the asl gene plays an important role in the replication of Brucella abortus in RAW-264.7 cells
physiological function
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the enzyme has a structural function in addition to its catalytic activity. The enzyme plays a more central role in cellular arginine utilization for NO synthesis beyond intracellular recycling of citrulline into arginine
physiological function
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the enzyme has a structural function in addition to its catalytic activity. The enzyme plays a more central role in cellular arginine utilization for NO synthesis beyond intracellular recycling of citrulline into arginine
physiological function
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the enzyme is required for arginine production for use in normal root elongation in rice
physiological function
as part of the urea cycle, the enzyme is essential for ammonia detoxification and L-arginine synthesis
physiological function
the arginine metabolic enzyme argininosuccinate lyase (ASL) promotes hepatocellular carcinoma formation in part via maintenance of cyclin A2 protein expression. Argininosuccinate lyase interacts with cyclin A2 in the cytoplasm and may promote phepatocellular carcinoma formation through this non-enzymatic function. Overexpression of ASL may be a contributing factor in drug resistance for arginine deprivation therapy
physiological function
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the asl gene plays an important role in the replication of Brucella abortus in RAW-264.7 cells
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additional information
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depleting arginine from the growth media by the addition of pegylated arginine deiminase decreases the production of argininosuccinate in FH-deficient cells and reduces cell survival and proliferation
additional information
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depleting arginine from the growth media by the addition of pegylated arginine deiminase decreases the production of argininosuccinate in FH-deficient cells and reduces cell survival and proliferation