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.[2]
A new 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.[3]
Regulation
It has been shown that in environments with high potassium concentrations, AMP-deaminase is regulated by ATP and ADP through a “Km-type” mechanism. In low potassium ion concentrations, a mixed “Km V-type” of the regulation is observed.[4]
↑Mahnke-Zizelman DK, Sabina RL (October 1992). "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. PMID1400401.
↑Skladanowski, Andrzej (1979). "Potassium-dependent regulation by ATP and ADP of AMP-deaminase from beef heart". International Journal of Biochemistry. 10 (2): 177–181. doi:10.1016/0020-711X(79)90114-9.
Further reading
Fishbein WN, Armbrustmacher VW, Griffin JL (1978). "Myoadenylate deaminase deficiency: a new disease of muscle". Science. 200 (4341): 545–8. doi:10.1126/science.644316. PMID644316.
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. PMID1370861.
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. PMID2345176.
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. PMID6167680.
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. PMID6406772.
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. PMID8335021.
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. PMID9443500.
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. PMID9730972.
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. PMID9880040.
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. PMID10086964.
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. PMID10996775.
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. PMID12117480.
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. PMID12213808.
