AMP deaminase explained

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

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.^[2]

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.^[3]

Pathology

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

Further reading

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

Notes and References

1. Mahnke-Zizelman DK, Sabina RL . Cloning of human AMP deaminase isoform E cDNAs. Evidence for a third AMPD gene exhibiting alternatively spliced 5'-exons . J. Biol. Chem. . 267 . 29 . 20866–77 . October 1992 . 10.1016/S0021-9258(19)36768-7 . 1400401 . free .
2. Ouyang J, Parakhia RA, Ochs RS . Metformin activates AMP kinase through inhibition of AMP deaminase . J. Biol. Chem. . 286 . 1 . 1–11 . January 2011 . 21059655 . 3012963 . 10.1074/jbc.M110.121806 . free .
3. Skladanowski. Andrzej. Potassium-dependent regulation by ATP and ADP of AMP-deaminase from beef heart. International Journal of Biochemistry. 1979. 10. 2. 177–181. 10.1016/0020-711X(79)90114-9. 428625.