CAD protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) is a trifunctional multi-domain enzyme involved in the first three steps of pyrimidine biosynthesis. De-novo synthesis starts with cytosolic carbamoylphosphate synthetase II which uses glutamine, carbon dioxide and ATP. This enzyme is inhibited by uridine triphosphate (feedback inhibition).
In 2015, the first observed pathological mutations of CAD were found in a four-year-old boy.[5]
CAD protein has been observed in the mid-piece of mammalian spermatozoa, among the mitochondria.[6]
^ abcGRCh38: Ensembl release 89: ENSG00000084774 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000013629 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Ng BG, Wolfe LA, Ichikawa M, Markello T, He M, Tifft CJ, et al. (June 2015). "Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors". Human Molecular Genetics. 24 (11): 3050–7. doi:10.1093/hmg/ddv057. PMC 4424951. PMID 25678555.
^Carrey EA, Dietz C, Glubb DM, Löffler M, Lucocq JM, Watson PF (June 2002). "Detection and location of the enzymes of de novo pyrimidine biosynthesis in mammalian spermatozoa". Reproduction. 123 (6): 757–68. doi:10.1530/rep.0.1230757. PMID 12052230.
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