Argininosuccinate synthase
Argininosuccinate synthase (ASS) (EC 6.3.4.5) is an enzyme that catalyzes the synthesis of argininosuccinate from citrulline and aspartate
ASS is responsible for the third step of the urea cycle and one of the reactions of the citrulline-NO cycle.
Gene
The gene that encodes for this enzyme, ASS, is located on chromosome 9. In humans, ASS is expressed mostly in the cells of liver and kidney.
Pathology
Citrullinemia: At least 50 mutations that cause type I citrullinemia have been identified in the ASS gene. Most of these mutations substitute one amino acid for another in ASS. These mutations likely affect the structure of the enzyme and its ability to bind to citrulline, aspartate, and other molecules. A few mutations lead to the production of an abnormally short enzyme that cannot effectively play its role in the urea cycle.
Defects in ASS disrupt the third step of the urea cycle, preventing the liver from processing excess nitrogen into urea. As a result, nitrogen (in the form of ammonia) and other byproducts of the urea cycle (such as citrulline) build up in the bloodstream. Ammonia is toxic, particularly to the nervous system. An accumulation of ammonia during the first few days of life leads to poor feeding, vomiting, seizures, and the other signs and symptoms of type I citrullinemia.
Treatment for this defect includes a low-protein diet and dietary supplementation with arginine and phenylacetate. Arginine allows the urea cycle to complete itself, creating the substrates needed to originally fix ammonia. This will lower blood pH. Additionally, phenylacetate reacts with backed-up glutamine, resulting on phenylacetoglutamine, which can be excreted renally.[2]
References
- ^ PDB 2nz2; Karlberg T, Collins R, van den Berg S, Flores A, Hammarström M, Högbom M, Holmberg Schiavone L, Uppenberg J (March 2008). "Structure of human argininosuccinate synthetase". Acta Crystallogr. D Biol. Crystallogr. 64 (Pt 3): 279–86. doi:10.1107/S0907444907067455. PMID 18323623.
- ^ Devlin, Thomas M. (2002). Textbook of biochemistry: with clinical correlations. New York: Wiley-Liss. pp. 788. ISBN 0-471-41136-1.
See also
External links
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| Main cycle |
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| Regulatory/transport |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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| 6.1: Carbon-Oxygen |
Aminoacyl tRNA synthetase ( Tyrosine, Tryptophan, Threonine, Leucine, Isoleucine, Lysine, Alanine, Valine, Methionine, Serine, Aspartate, D-alanine-poly(phosphoribitol) ligase, Glycine, Proline, Cysteine, Glutamate, Glutamine, Arginine, Phenylalanine, Histidine, Asparagine, Aspartate, Glutamate, Lysine)
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| 6.2: Carbon-Sulfur |
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| 6.3: Carbon-Nitrogen |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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| Biotin dependent carboxylase |
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| Other |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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| 6.5: Phosphoric Ester |
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| 6.6: Nitrogen-Metal |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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