AMP deaminase

AMP deaminase 1 is an enzyme that in humans is encoded by the AMPD1 gene.

AMPD1
Identifiers
Aliases	AMPD1, MAD, MADA, MMDD, adenosine monophosphate deaminase 1, AMP deaminase, AMPD
External IDs	OMIM: 102770; MGI: 88015; HomoloGene: 20; GeneCards: AMPD1; OMA:AMPD1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p13.2 Start 114,673,090 bp End 114,695,618 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3 F2.2|3 45.25 cM Start 102,981,330 bp End 103,007,036 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in triceps brachii muscle vastus lateralis muscle Skeletal muscle tissue of rectus abdominis biceps brachii glutes Skeletal muscle tissue of biceps brachii muscle of thigh thoracic diaphragm deltoid muscle gastrocnemius muscle Top expressed in quadriceps femoris muscle muscle of thigh skeletal muscle tissue zone of skin esophagus lip thymus embryo zygote blastocyst More reference expression data BioGPS More reference expression data
Gene ontology Molecular function hydrolase activity myosin heavy chain binding metal ion binding deaminase activity AMP deaminase activity Cellular component cytosol Biological process response to organic substance IMP salvage nucleotide metabolic process purine-containing compound salvage purine ribonucleoside monophosphate biosynthetic process IMP biosynthetic process AMP metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 270 229665 Ensembl ENSG00000116748 ENSMUSG00000070385 UniProt P23109 Q3V1D3 RefSeq (mRNA) NM_001172626 NM_000036 NM_001033303 RefSeq (protein) NP_000027 NP_001166097 NP_001028475 Location (UCSC) Chr 1: 114.67 – 114.7 Mb Chr 3: 102.98 – 103.01 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Adenosine monophosphate deaminase is an enzyme that converts adenosine monophosphate (AMP) to inosine monophosphate (IMP), freeing an ammonia molecule in the process.

Function

Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine nucleotide cycle. Two other genes have been identified, AMPD2 and AMPD3, for the liver- and erythrocyte-specific isoforms, respectively. Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in the human.

A research report shows that the widely prescribed diabetes medication metformin works on AMP-activated kinase (AMPK) by directly inhibiting AMP deaminase, thereby increasing cellular AMP.

Regulation

It has been shown that in environments with high potassium concentrations, AMP-deaminase is regulated by ATP and ADP through a “K_m-type” mechanism. In low potassium ion concentrations, a mixed “K_m V-type” of the regulation is observed.

Pathology

AMPD1 deficiency, also known as myoadenylate deaminase deficiency, is a disorder in which the body produces insufficient AMP deaminase.

• 
  adenosine monophosphate (AMP)
• 
  inosine monophosphate (IMP)

Further reading

• Fishbein WN, Armbrustmacher VW, Griffin JL (1978). "Myoadenylate deaminase deficiency: a new disease of muscle". Science. 200 (4341): 545–8. Bibcode:1978Sci...200..545F. doi:10.1126/science.644316. PMID 644316.
• Sabina RL, Fishbein WN, Pezeshkpour G, et al. (1992). "Molecular analysis of the myoadenylate deaminase deficiencies". Neurology. 42 (1): 170–9. doi:10.1212/wnl.42.1.170. PMID 1370861. S2CID 11221341.
• Morisaki T, Gross M, Morisaki H, et al. (1992). "Molecular basis of AMP deaminase deficiency in skeletal muscle". Proc. Natl. Acad. Sci. U.S.A. 89 (14): 6457–61. Bibcode:1992PNAS...89.6457M. doi:10.1073/pnas.89.14.6457. PMC 49520. PMID 1631143.
• Sabina RL, Morisaki T, Clarke P, et al. (1990). "Characterization of the human and rat myoadenylate deaminase genes". J. Biol. Chem. 265 (16): 9423–33. doi:10.1016/S0021-9258(19)38866-0. PMID 2345176.
• Dale GL (1989). "Radioisotopic assay for erythrocyte adenosine 5'-monophosphate deaminase". Clin. Chim. Acta. 182 (1): 1–7. doi:10.1016/0009-8981(89)90144-7. PMID 2502331.
• Mercelis R, Martin JJ, Dehaene I, et al. (1981). "Myoadenylate deaminase deficiency in a patient with facial and limb girdle myopathy". J. Neurol. 225 (3): 157–66. doi:10.1007/BF00313744. PMID 6167680. S2CID 29588220.
• van Laarhoven JP, de Gast GC, Spierenburg GT, de Bruyn CH (1983). "Enzymological studies in chronic lymphocytic leukemia". Leuk. Res. 7 (2): 261–7. doi:10.1016/0145-2126(83)90016-4. PMID 6406772.
• Kelemen J, Rice DR, Bradley WG, et al. (1982). "Familial myoadenylate deaminase deficiency and exertional myalgia". Neurology. 32 (8): 857–63. doi:10.1212/wnl.32.8.857. PMID 7201581. S2CID 39331402.
• Baumeister FA, Gross M, Wagner DR, et al. (1993). "Myoadenylate deaminase deficiency with severe rhabdomyolysis". Eur. J. Pediatr. 152 (6): 513–5. doi:10.1007/BF01955062. PMID 8335021. S2CID 32249030.
• Morisaki T, Holmes EW (1993). "Functionally distinct elements are required for expression of the AMPD1 gene in myocytes". Mol. Cell. Biol. 13 (9): 5854–60. doi:10.1128/MCB.13.9.5854. PMC 360332. PMID 8355716.
• Bruno C, Minetti C, Shanske S, et al. (1998). "Combined defects of muscle phosphofructokinase and AMP deaminase in a child with myoglobinuria". Neurology. 50 (1): 296–8. doi:10.1212/wnl.50.1.296. PMID 9443500. S2CID 23521698.
• Hisatome I, Morisaki T, Kamma H, et al. (1998). "Control of AMP deaminase 1 binding to myosin heavy chain". Am. J. Physiol. 275 (3 Pt 1): C870–81. doi:10.1152/ajpcell.1998.275.3.C870. PMID 9730972.
• Sims B, Powers RE, Sabina RL, Theibert AB (1999). "Elevated adenosine monophosphate deaminase activity in Alzheimer's disease brain". Neurobiol. Aging. 19 (5): 385–91. doi:10.1016/S0197-4580(98)00083-9. PMID 9880040. S2CID 23996226.
• Loh E, Rebbeck TR, Mahoney PD, et al. (1999). "Common variant in AMPD1 gene predicts improved clinical outcome in patients with heart failure". Circulation. 99 (11): 1422–5. doi:10.1161/01.cir.99.11.1422. PMID 10086964.
• Abe M, Higuchi I, Morisaki H, et al. (2000). "Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient". Neuromuscul. Disord. 10 (7): 472–7. doi:10.1016/S0960-8966(00)00127-9. PMID 10996775. S2CID 21449661.
• Morisaki H, Higuchi I, Abe M, et al. (2001). "First missense mutations (R388W and R425H) of AMPD1 accompanied with myopathy found in a Japanese patient". Hum. Mutat. 16 (6): 467–72. doi:10.1002/1098-1004(200012)16:6<467::AID-HUMU3>3.0.CO;2-V. PMID 11102975. S2CID 32543488.
• Gross M, Rötzer E, Kölle P, et al. (2002). "A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population". Neuromuscul. Disord. 12 (6): 558–65. doi:10.1016/S0960-8966(02)00008-1. PMID 12117480. S2CID 8380610.
• Mahnke-Zizelman DK, Sabina RL (2003). "N-terminal sequence and distal histidine residues are responsible for pH-regulated cytoplasmic membrane binding of human AMP deaminase isoform E." J. Biol. Chem. 277 (45): 42654–62. doi:10.1074/jbc.M203473200. PMID 12213808.

External links

• AMP+Deaminase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human AMPD1 genome location and AMPD1 gene details page in the UCSC Genome Browser.