Argininosuccinate synthetase 1

{{Short description|Protein-coding gene in the species Homo sapiens}}

Argininosuccinate synthetase is an enzyme that in humans is encoded by the ASS1 gene.{{cite book | vauthors = Beaudet AL, O'Brien WE, Bock HG, Freytag SO, Su TS | title = Advances in Human Genetics 15 | chapter = The Human Argininosuccinate Synthetase Locus and Citrullinemia | volume = 15 | pages = 161–96, 291–2 |date=Mar 1986 | pmid = 3513483 | doi = 10.1007/978-1-4615-8356-1_3| isbn = 978-1-4615-8358-5 }}{{cite journal | vauthors = Carritt B, Goldfarb PS, Hooper ML, Slack C | title = Chromosome assignment of a human gene for argininosuccinate synthetase expression in Chinese hamsterxhuman somatic cell hybrids | journal = Experimental Cell Research | volume = 106 | issue = 1 | pages = 71–78 | date = April 1977 | pmid = 852520 | doi = 10.1016/0014-4827(77)90242-7 }}{{cite web | title = Entrez Gene: ASS1 argininosuccinate synthetase 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=445}}

The protein encoded by this gene catalyzes the penultimate step of the arginine biosynthetic pathway. There are approximately 10 to 14 copies of this gene including the pseudogenes scattered across the human genome, among which the one located on chromosome 9 appears to be the only functional gene for argininosuccinate synthetase. Two transcript variants encoding the same protein have been found for this gene.

Clinical significance

Mutations in the chromosome 9 copy of ASS cause citrullinemia.

Arginine is considered a non-essential amino acid since normal cells can synthesize it from citrulline and aspartate using the enzymes argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL). Consequently, depleting arginine can be an effective therapeutic approach. Notably, over 70% of tumors show reduced ASS1 transcription, making these cancer cells reliant on external sources of arginine, which forms the basis of arginine-deprivation therapy.{{cite journal | vauthors = Chen CL, Hsu SC, Ann DK, Yen Y, Kung HJ | title = Arginine Signaling and Cancer Metabolism | journal = Cancers | volume = 13 | issue = 14 | date = July 2021 | page = 3541 | pmid = 34298755 | pmc = 8306961 | doi = 10.3390/cancers13143541 | doi-access = free }}

The investigational drug pegargiminase that degrades arginine is currently in trials for the treatment of ASS1 deficient cancers.{{cite journal | vauthors = Field GC, Pavlyk I, Szlosarek PW | title = Bench-to-Bedside Studies of Arginine Deprivation in Cancer | journal = Molecules | location = Basel, Switzerland | volume = 28 | issue = 5 | date = February 2023 | page = 2150 | pmid = 36903394 | pmc = 10005060 | doi = 10.3390/molecules28052150 | doi-access = free }}

References

{{cite journal | vauthors = Ikeda S | title = [Recent advances of the treatment in metabolic disorders] | journal = Rinsho Shinkeigaku = Clinical Neurology | volume = 40 | issue = 12 | pages = 1264–1266 | date = December 2000 | pmid = 11464474 }}
{{cite journal | vauthors = Carritt B | title = Somatic cell genetic evidence for the presence of a gene for citrullinemia on human chromosome 9 | journal = Cytogenetics and Cell Genetics | volume = 19 | issue = 1 | pages = 44–48 | year = 1977 | pmid = 891260 | doi = 10.1159/000130793 }}
{{cite journal | vauthors = Dhanakoti SN, Brosnan ME, Herzberg GR, Brosnan JT | title = Cellular and subcellular localization of enzymes of arginine metabolism in rat kidney | journal = The Biochemical Journal | volume = 282 ( Pt 2) | issue = Pt 2 | pages = 369–375 | date = March 1992 | pmid = 1312326 | pmc = 1130788 | doi = 10.1042/bj2820369 }}
{{cite journal | vauthors = Wakui H, Komatsuda A, Itoh H, Kobayashi R, Nakamoto Y, Miura AB | title = Renal argininosuccinate synthetase: purification, immunohistochemical localization, and elastin-binding property | journal = Renal Physiology and Biochemistry | volume = 15 | issue = 1 | pages = 1–9 | year = 1992 | pmid = 1372742 | doi = 10.1159/000173435 }}
{{cite journal | vauthors = Kobayashi K, Rosenbloom C, Beaudet AL, O'Brien WE | title = Additional mutations in argininosuccinate synthetase causing citrullinemia | journal = Molecular Biology & Medicine | volume = 8 | issue = 1 | pages = 95–100 | date = February 1991 | pmid = 1943692 }}
{{cite journal | vauthors = Kobayashi K, Jackson MJ, Tick DB, O'Brien WE, Beaudet AL | title = Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia | journal = The Journal of Biological Chemistry | volume = 265 | issue = 19 | pages = 11361–11367 | date = July 1990 | pmid = 2358466 | doi = 10.1016/S0021-9258(19)38601-6 | doi-access = free }}
{{cite journal | vauthors = Isashiki Y, Noda T, Kobayashi K, Sase M, Saheki T, Titani K | title = Identification of essential arginine residue(s) for Mg-ATP binding of human argininosuccinate synthetase | journal = Protein Sequences & Data Analysis | volume = 2 | issue = 4 | pages = 283–287 | date = July 1989 | pmid = 2788888 }}
{{cite journal | vauthors = Jinno Y, Nomiyama H, Matuo S, Shimada K, Matsuda I, Saheki T | title = Structure of the 5' end region of the human argininosuccinate synthetase gene | journal = Journal of Inherited Metabolic Disease | volume = 8 | issue = 3 | pages = 157–159 | year = 1987 | pmid = 3027451 | doi = 10.1007/BF01819307 | s2cid = 32917363 }}
{{cite journal | vauthors = Freytag SO, Beaudet AL, Bock HG, O'Brien WE | title = Molecular structure of the human argininosuccinate synthetase gene: occurrence of alternative mRNA splicing | journal = Molecular and Cellular Biology | volume = 4 | issue = 10 | pages = 1978–1984 | date = October 1984 | pmid = 6095035 | pmc = 369014 | doi = 10.1128/mcb.4.10.1978 }}
{{cite journal | vauthors = Bock HG, Su TS, O'Brien WE, Beaudet AL | title = Sequence for human argininosuccinate synthetase cDNA | journal = Nucleic Acids Research | volume = 11 | issue = 18 | pages = 6505–6512 | date = September 1983 | pmid = 6194510 | pmc = 326390 | doi = 10.1093/nar/11.18.6505 }}
{{cite journal | vauthors = Freytag SO, Bock HG, Beaudet AL, O'Brien WE | title = Molecular structures of human argininosuccinate synthetase pseudogenes. Evolutionary and mechanistic implications | journal = The Journal of Biological Chemistry | volume = 259 | issue = 5 | pages = 3160–3166 | date = March 1984 | pmid = 6321498 | doi = 10.1016/S0021-9258(17)43275-3 | doi-access = free }}
{{cite journal | vauthors = Kobayashi K, Kakinoki H, Fukushige T, Shaheen N, Terazono H, Saheki T | title = Nature and frequency of mutations in the argininosuccinate synthetase gene that cause classical citrullinemia | journal = Human Genetics | volume = 96 | issue = 4 | pages = 454–463 | date = October 1995 | pmid = 7557970 | doi = 10.1007/BF00191806 | s2cid = 861085 }}
{{cite journal | vauthors = Kobayashi K, Shaheen N, Terazono H, Saheki T | title = Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia | journal = American Journal of Human Genetics | volume = 55 | issue = 6 | pages = 1103–1112 | date = December 1994 | pmid = 7977368 | pmc = 1918437 }}
{{cite journal | vauthors = Shaheen N, Kobayashi K, Terazono H, Fukushige T, Horiuchi M, Saheki T | title = Characterization of human wild-type and mutant argininosuccinate synthetase proteins expressed in bacterial cells | journal = Enzyme & Protein | volume = 48 | issue = 5-6 | pages = 251–264 | year = 1996 | pmid = 8792870 | doi = 10.1159/000474998 }}
{{cite journal | vauthors = Gress TM, Müller-Pillasch F, Geng M, Zimmerhackl F, Zehetner G, Friess H, Büchler M, Adler G, Lehrach H | title = A pancreatic cancer-specific expression profile | journal = Oncogene | volume = 13 | issue = 8 | pages = 1819–1830 | date = October 1996 | pmid = 8895530 }}
{{cite journal | vauthors = Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ | title = A two-dimensional gel database of human colon carcinoma proteins | journal = Electrophoresis | volume = 18 | issue = 3-4 | pages = 605–613 | year = 1997 | pmid = 9150948 | doi = 10.1002/elps.1150180344 | s2cid = 25454450 }}

External links

{{UCSC gene info|ASS1}}

Argininosuccinate synthetase 1

Clinical significance

References

Further reading

Further reading

External links