AMP deaminase 1

AMPD1
Identifiers
Aliases	AMPD1, MAD, MADA, MMDD, adenosine monophosphate deaminase 1, AMP deaminase, AMPD
External IDs	OMIM: 102770; MGI: 88015; GeneCards: AMPD1
Enzyme activity
Gene location (Human)
Chr.	Chromosome 1 (human)
End	114,695,618 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	103,007,036 bp
RNA expression pattern
	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
	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
Databases	NCBI: entry; OMA: entry
	270
	229665
	ENSG00000116748
	ENSMUSG00000070385
	P23109
	Q3V1D3
	NM_001172626; NM_000036
	NM_001033303
	NP_000027; NP_001166097
	NP_001028475
	Wikidata
View/Edit Human	View/Edit Mouse

AMP deaminase 1 is an enzyme that in humans is encoded by the AMPD1 gene (previously AMPD). It converts adenosine monophosphate (AMP) to inosinic acid and ammonia:

adenosine monophosphate

H₂O

NH₃

Rightward reaction arrow with minor substrate(s) from top left and minor product(s) to top right

inosinic acid

Function

Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to inosinic acid in skeletal muscle and plays an important role in the purine nucleotide cycle. AMPD1 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.

AMP deaminases

Enzymes that catalyze the deamination of AMP to inosinic acid are called AMP deaminases (EC 3.5.4.6). In humans, AMPD1 encodes the skeletal muscle isozyme, while two other genes have been identified, AMPD2 and AMPD3, for the liver- and erythrocyte-specific isoforms, respectively.

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.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000116748 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000070385 – 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.
↑ 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". The Journal of Biological Chemistry. 267 (29): 20866–20877. doi:10.1016/S0021-9258(19)36768-7. PMID 1400401.
1 2 3 EntrezGene 270
↑ Zabielska MA, Borkowski T, Slominska EM, Smolenski RT (August 2015). "Inhibition of AMP deaminase as therapeutic target in cardiovascular pathology". Pharmacological Reports. 67 (4): 682–688. doi:10.1016/j.pharep.2015.04.007. PMID 26321268.
↑ Ouyang J, Parakhia RA, Ochs RS (January 2011). "Metformin activates AMP kinase through inhibition of AMP deaminase". The Journal of Biological Chemistry. 286 (1): 1–11. doi:10.1074/jbc.M110.121806. PMC 3012963. PMID 21059655.
↑ (EC 3.5.4.6)
↑ Składanowski A, Kaletha K, Zydowo M (1979). "Potassium-dependent regulation by ATP and ADP of AMP-deaminase from beef heart". The International Journal of Biochemistry. 10 (2): 177–181. doi:10.1016/0020-711X(79)90114-9. PMID 428625.
↑ Ehlers L, Meyts I (May 2025). "Getting to know adenosine deaminase 2 deficiency inside and out". The Journal of Allergy and Clinical Immunology. 155 (5): 1451–1463. doi:10.1016/j.jaci.2025.01.040. PMC 12060026. PMID 39956283.

Fishbein WN, Armbrustmacher VW, Griffin JL (1978). "Myoadenylate deaminase deficiency: a new disease of muscle". Science. 200 (4341). New York, N.Y.: 545–548. Bibcode:1978Sci...200..545F. doi:10.1126/science.644316. PMID 644316.
Sabina RL, Fishbein WN, Pezeshkpour G, Clarke PR, Holmes EW (January 1992). "Molecular analysis of the myoadenylate deaminase deficiencies". Neurology. 42 (1): 170–179. doi:10.1212/wnl.42.1.170. PMID 1370861. S2CID 11221341.
Morisaki T, Gross M, Morisaki H, Pongratz D, Zöllner N, Holmes EW (July 1992). "Molecular basis of AMP deaminase deficiency in skeletal muscle". Proceedings of the National Academy of Sciences of the United States of America. 89 (14): 6457–6461. Bibcode:1992PNAS...89.6457M. doi:10.1073/pnas.89.14.6457. PMC 49520. PMID 1631143.
Sabina RL, Morisaki T, Clarke P, Eddy R, Shows TB, Morton CC, et al. (June 1990). "Characterization of the human and rat myoadenylate deaminase genes". The Journal of Biological Chemistry. 265 (16): 9423–9433. doi:10.1016/S0021-9258(19)38866-0. PMID 2345176.
Dale GL (June 1989). "Radioisotopic assay for erythrocyte adenosine 5'-monophosphate deaminase". Clinica Chimica Acta; International Journal of Clinical Chemistry. 182 (1): 1–7. doi:10.1016/0009-8981(89)90144-7. PMID 2502331.
Mercelis R, Martin JJ, Dehaene I, de Barsy T, Van den Berghe G (1981). "Myoadenylate deaminase deficiency in a patient with facial and limb girdle myopathy". Journal of Neurology. 225 (3): 157–166. 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". Leukemia Research. 7 (2): 261–267. doi:10.1016/0145-2126(83)90016-4. PMID 6406772.
Kelemen J, Rice DR, Bradley WG, Munsat TL, DiMauro S, Hogan EL (August 1982). "Familial myoadenylate deaminase deficiency and exertional myalgia". Neurology. 32 (8): 857–863. doi:10.1212/wnl.32.8.857. PMID 7201581. S2CID 39331402.
Baumeister FA, Gross M, Wagner DR, Pongratz D, Eife R (June 1993). "Myoadenylate deaminase deficiency with severe rhabdomyolysis". European Journal of Pediatrics. 152 (6): 513–515. 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". Molecular and Cellular Biology. 13 (9): 5854–5860. doi:10.1128/MCB.13.9.5854. PMC 360332. PMID 8355716.
Bruno C, Minetti C, Shanske S, Morreale G, Bado M, Cordone G, et al. (January 1998). "Combined defects of muscle phosphofructokinase and AMP deaminase in a child with myoglobinuria". Neurology. 50 (1): 296–298. doi:10.1212/wnl.50.1.296. PMID 9443500. S2CID 23521698.
Hisatome I, Morisaki T, Kamma H, Sugama T, Morisaki H, Ohtahara A, et al. (September 1998). "Control of AMP deaminase 1 binding to myosin heavy chain". The American Journal of Physiology. 275 (3): 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". Neurobiology of Aging. 19 (5): 385–391. doi:10.1016/S0197-4580(98)00083-9. PMID 9880040. S2CID 23996226.
Loh E, Rebbeck TR, Mahoney PD, DeNofrio D, Swain JL, Holmes EW (March 1999). "Common variant in AMPD1 gene predicts improved clinical outcome in patients with heart failure". Circulation. 99 (11): 1422–1425. doi:10.1161/01.cir.99.11.1422. PMID 10086964.
Abe M, Higuchi I, Morisaki H, Morisaki T, Osame M (October 2000). "Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient". Neuromuscular Disorders. 10 (7): 472–477. doi:10.1016/S0960-8966(00)00127-9. PMID 10996775. S2CID 21449661.
Morisaki H, Higuchi I, Abe M, Osame M, Morisaki T (December 2000). "First missense mutations (R388W and R425H) of AMPD1 accompanied with myopathy found in a Japanese patient". Human Mutation. 16 (6): 467–472. 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, Mortier W, Reichmann H, Goebel HH, et al. (August 2002). "A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population". Neuromuscular Disorders. 12 (6): 558–565. 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." The Journal of Biological Chemistry. 277 (45): 42654–42662. 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.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000116748 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000070385 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Mahnke-Zizelman_1992-5] 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". The Journal of Biological Chemistry. 267 (29): 20866–20877. doi:10.1016/S0021-9258(19)36768-7. PMID 1400401.

[entrez-6] 1 2 3 EntrezGene 270

[7] Zabielska MA, Borkowski T, Slominska EM, Smolenski RT (August 2015). "Inhibition of AMP deaminase as therapeutic target in cardiovascular pathology". Pharmacological Reports. 67 (4): 682–688. doi:10.1016/j.pharep.2015.04.007. PMID 26321268.

[Ouyang_2011-8] Ouyang J, Parakhia RA, Ochs RS (January 2011). "Metformin activates AMP kinase through inhibition of AMP deaminase". The Journal of Biological Chemistry. 286 (1): 1–11. doi:10.1074/jbc.M110.121806. PMC 3012963. PMID 21059655.

[9] (EC 3.5.4.6)

[10] Składanowski A, Kaletha K, Zydowo M (1979). "Potassium-dependent regulation by ATP and ADP of AMP-deaminase from beef heart". The International Journal of Biochemistry. 10 (2): 177–181. doi:10.1016/0020-711X(79)90114-9. PMID 428625.

[11] Ehlers L, Meyts I (May 2025). "Getting to know adenosine deaminase 2 deficiency inside and out". The Journal of Allergy and Clinical Immunology. 155 (5): 1451–1463. doi:10.1016/j.jaci.2025.01.040. PMC 12060026. PMID 39956283.

v t e Hydrolases: carbon-nitrogen non-peptide (EC 3.5)
3.5.1: Linear amides / Amidohydrolases	Asparaginase Glutaminase Urease Biotinidase Aminoacylase ACY1 Aspartoacylase(ACY2) ACY3 Ceramidase Aspartylglucosaminidase Fatty acid amide hydrolase Histone deacetylase Sirtuin
3.5.2: Cyclic amides/ Amidohydrolases	Barbiturase Beta-lactamase Dihydroorotase
3.5.3: Linear amidines/ Ureohydrolases	Arginase Agmatinase Protein-arginine deiminase
3.5.4: Cyclic amidines/ Aminohydrolases	Guanine deaminase Adenosine deaminase AMP deaminase Inosine monophosphate synthase DCMP deaminase GTP cyclohydrolase I Cytidine deaminase AICDA Activation-induced cytidine deaminase
3.5.5: Nitriles/ Aminohydrolases	Nitrilase
3.5.99: Other	Riboflavinase Thiaminase II

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)