AMP deaminase

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.{{cite journal | vauthors = Ouyang J, Parakhia RA, Ochs RS | title = Metformin activates AMP kinase through inhibition of AMP deaminase | journal = J. Biol. Chem. | volume = 286 | issue = 1 | pages = 1–11 |date=January 2011 | pmid = 21059655 | pmc = 3012963 | doi = 10.1074/jbc.M110.121806 | doi-access = free }}

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.{{cite journal|last1=Skladanowski|first1=Andrzej|title=Potassium-dependent regulation by ATP and ADP of AMP-deaminase from beef heart|journal=International Journal of Biochemistry|date=1979|volume=10|issue=2|pages=177–181|doi=10.1016/0020-711X(79)90114-9|pmid=428625}}

==Pathology==

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

Image:Adenosinmonophosphat protoniert.svg|adenosine monophosphate (AMP)

Image:inosinic acid structure.svg|inosine monophosphate (IMP)

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• {{cite journal | vauthors=Fishbein WN, Armbrustmacher VW, Griffin JL |title=Myoadenylate deaminase deficiency: a new disease of muscle. |journal=Science |volume=200 |issue= 4341 |pages= 545–8 |year= 1978 |pmid= 644316 |doi=10.1126/science.644316 |bibcode=1978Sci...200..545F }}
• {{cite journal | vauthors=Sabina RL, Fishbein WN, Pezeshkpour G |title=Molecular analysis of the myoadenylate deaminase deficiencies. |journal=Neurology |volume=42 |issue= 1 |pages= 170–9 |year= 1992 |pmid= 1370861 |doi= 10.1212/wnl.42.1.170|s2cid=11221341 |display-authors=etal}}
• {{cite journal | vauthors=Morisaki T, Gross M, Morisaki H |title=Molecular basis of AMP deaminase deficiency in skeletal muscle. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 14 |pages= 6457–61 |year= 1992 |pmid= 1631143 |doi=10.1073/pnas.89.14.6457 | pmc=49520 |bibcode=1992PNAS...89.6457M |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Sabina RL, Morisaki T, Clarke P |title=Characterization of the human and rat myoadenylate deaminase genes. |journal=J. Biol. Chem. |volume=265 |issue= 16 |pages= 9423–33 |year= 1990 |doi=10.1016/S0021-9258(19)38866-0 |pmid= 2345176 |display-authors=etal|doi-access=free }}
• {{cite journal | author=Dale GL |title=Radioisotopic assay for erythrocyte adenosine 5'-monophosphate deaminase. |journal=Clin. Chim. Acta |volume=182 |issue= 1 |pages= 1–7 |year= 1989 |pmid= 2502331 |doi=10.1016/0009-8981(89)90144-7 }}
• {{cite journal | vauthors=Mercelis R, Martin JJ, Dehaene I |title=Myoadenylate deaminase deficiency in a patient with facial and limb girdle myopathy. |journal=J. Neurol. |volume=225 |issue= 3 |pages= 157–66 |year= 1981 |pmid= 6167680 |doi=10.1007/BF00313744 |s2cid=29588220 |display-authors=etal}}
• {{cite journal | vauthors=van Laarhoven JP, de Gast GC, Spierenburg GT, de Bruyn CH |title=Enzymological studies in chronic lymphocytic leukemia. |journal=Leuk. Res. |volume=7 |issue= 2 |pages= 261–7 |year= 1983 |pmid= 6406772 |doi=10.1016/0145-2126(83)90016-4 }}
• {{cite journal | vauthors=Kelemen J, Rice DR, Bradley WG |title=Familial myoadenylate deaminase deficiency and exertional myalgia. |journal=Neurology |volume=32 |issue= 8 |pages= 857–63 |year= 1982 |pmid= 7201581 |doi= 10.1212/wnl.32.8.857|s2cid=39331402 |display-authors=etal}}
• {{cite journal | vauthors=Baumeister FA, Gross M, Wagner DR |title=Myoadenylate deaminase deficiency with severe rhabdomyolysis. |journal=Eur. J. Pediatr. |volume=152 |issue= 6 |pages= 513–5 |year= 1993 |pmid= 8335021 |doi=10.1007/BF01955062 |s2cid=32249030 |display-authors=etal}}
• {{cite journal | vauthors=Morisaki T, Holmes EW |title=Functionally distinct elements are required for expression of the AMPD1 gene in myocytes. |journal=Mol. Cell. Biol. |volume=13 |issue= 9 |pages= 5854–60 |year= 1993 |pmid= 8355716 |doi= 10.1128/MCB.13.9.5854| pmc=360332 }}
• {{cite journal | vauthors=Bruno C, Minetti C, Shanske S |title=Combined defects of muscle phosphofructokinase and AMP deaminase in a child with myoglobinuria. |journal=Neurology |volume=50 |issue= 1 |pages= 296–8 |year= 1998 |pmid= 9443500 |doi= 10.1212/wnl.50.1.296|s2cid=23521698 |display-authors=etal}}
• {{cite journal | vauthors=Hisatome I, Morisaki T, Kamma H |title=Control of AMP deaminase 1 binding to myosin heavy chain. |journal=Am. J. Physiol. |volume=275 |issue= 3 Pt 1 |pages= C870–81 |year= 1998 |pmid= 9730972 |doi= 10.1152/ajpcell.1998.275.3.C870|display-authors=etal}}
• {{cite journal | vauthors=Sims B, Powers RE, Sabina RL, Theibert AB |title=Elevated adenosine monophosphate deaminase activity in Alzheimer's disease brain. |journal=Neurobiol. Aging |volume=19 |issue= 5 |pages= 385–91 |year= 1999 |pmid= 9880040 |doi=10.1016/S0197-4580(98)00083-9 |s2cid=23996226 }}
• {{cite journal | vauthors=Loh E, Rebbeck TR, Mahoney PD |title=Common variant in AMPD1 gene predicts improved clinical outcome in patients with heart failure. |journal=Circulation |volume=99 |issue= 11 |pages= 1422–5 |year= 1999 |pmid= 10086964 |doi= 10.1161/01.cir.99.11.1422|display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Abe M, Higuchi I, Morisaki H |title=Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient. |journal=Neuromuscul. Disord. |volume=10 |issue= 7 |pages= 472–7 |year= 2000 |pmid= 10996775 |doi=10.1016/S0960-8966(00)00127-9 |s2cid=21449661 |display-authors=etal}}
• {{cite journal | vauthors=Morisaki H, Higuchi I, Abe M |title=First missense mutations (R388W and R425H) of AMPD1 accompanied with myopathy found in a Japanese patient. |journal=Hum. Mutat. |volume=16 |issue= 6 |pages= 467–72 |year= 2001 |pmid= 11102975 |doi= 10.1002/1098-1004(200012)16:6<467::AID-HUMU3>3.0.CO;2-V |s2cid=32543488 |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Gross M, Rötzer E, Kölle P |title=A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population. |journal=Neuromuscul. Disord. |volume=12 |issue= 6 |pages= 558–65 |year= 2002 |pmid= 12117480 |doi=10.1016/S0960-8966(02)00008-1 |s2cid=8380610 |display-authors=etal}}
• {{cite journal | vauthors=Mahnke-Zizelman DK, Sabina RL |title=N-terminal sequence and distal histidine residues are responsible for pH-regulated cytoplasmic membrane binding of human AMP deaminase isoform E. |journal=J. Biol. Chem. |volume=277 |issue= 45 |pages= 42654–62 |year= 2003 |pmid= 12213808 |doi= 10.1074/jbc.M203473200 |doi-access= free }}

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• {{MeshName|AMP+Deaminase}}
• {{UCSC gene info|AMPD1}}

{{Nucleotide metabolism}}

{{Carbon-nitrogen non-peptide hydrolases}}

{{Enzymes}}

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Category:EC 3.5.4

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