Decarboxylases | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY

Decarboxylases C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The decarboxylases generate CO₂ and the indicated products from acidic substrates, requiring pyridoxal 5-phosphate or pyruvic acid as a co-factor.

Enzymes

1269

GAD1 (Glutamic acid decarboxylase 1) C Show summary »« Hide summary

Target Id

1272

Nomenclature

Glutamic acid decarboxylase 1

Common abbreviation

GAD1

Previous and unofficial names

GAD1 (GAD65) | Gad67 | GAD | GAD25 | GAD44 | GAD-67 | glutamate decarboxylase 1 | Glutamate decarboxylase 1 (brain) | glutamate decarboxylase 1 (brain, 67kDa)

Genes

GAD1 (Hs), Gad1 (Mm), Gad1 (Rn)

Ensembl ID

ENSG00000128683 (Hs), ENSMUSG00000070880 (Mm), ENSRNOG00000000007 (Rn)

UniProtKB AC

Q99259 (Hs), P48318 (Mm), P18088 (Rn)

EC number

4.1.1.15

L-glutamic acid + H⁺ -> GABA + CO₂

Endogenous substrates

L-glutamic acid

L-aspartic acid

Products

GABA

Cofactors

pyridoxal 5-phosphate

Selective inhibitors

s-allylglycine

Comment

L-aspartic acid is a less rapidly metabolised substrate of mouse brain glutamic acid decarboxylase generating β-alanine [9]. Autoantibodies against GAD1 and GAD2 are elevated in type 1 diabetes mellitus and neurological disorders (see Further reading).

GAD2 (Glutamic acid decarboxylase 2) C Show summary »« Hide summary

Target Id

1273

Nomenclature

Glutamic acid decarboxylase 2

Common abbreviation

GAD2

Previous and unofficial names

Genes

GAD2 (Hs), Gad2 (Mm), Gad2 (Rn)

Ensembl ID

ENSG00000136750 (Hs), ENSMUSG00000026787 (Mm), ENSRNOG00000018200 (Rn)

UniProtKB AC

Q05329 (Hs), P48320 (Mm), Q05683 (Rn)

EC number

4.1.1.15

L-glutamic acid + H⁺ -> GABA + CO₂

Endogenous substrates

L-glutamic acid

L-aspartic acid

Products

GABA

Cofactors

pyridoxal 5-phosphate

Selective inhibitors

s-allylglycine

Comment

HDC (Histidine decarboxylase) C Show summary »« Hide summary

ADC (L-Arginine decarboxylase ) C Show summary »« Hide summary

Target Id

1270

Nomenclature

L-Arginine decarboxylase

Common abbreviation

ADC

Previous and unofficial names

Genes

AZIN2 (Hs), Azin2 (Mm), Azin2 (Rn)

Ensembl ID

ENSG00000142920 (Hs), ENSMUSG00000028789 (Mm), ENSRNOG00000051507 (Rn)

UniProtKB AC

Q96A70 (Hs), Q8BVM4 (Mm)

EC number

4.1.1.19

Endogenous substrates

L-arginine

Products

agmatine [10]

Cofactors

pyridoxal 5-phosphate

Comment

The presence of a functional ADC activity in human tissues has been questioned [1].

AADC (L-Aromatic amino-acid decarboxylase ) C Show summary »« Hide summary More detailed page go icon to follow link

MLYCD (Malonyl-CoA decarboxylase) C Show summary »« Hide summary More detailed page go icon to follow link

ODC (Ornithine decarboxylase) C Show summary »« Hide summary More detailed page go icon to follow link

PSDC (Phosphatidylserine decarboxylase ) C Show summary »« Hide summary

SAMDC (S-Adenosylmethionine decarboxylase ) C Show summary »« Hide summary

Target Id

1269

Nomenclature

S-Adenosylmethionine decarboxylase

Common abbreviation

SAMDC

Previous and unofficial names

Genes

AMD1 (Hs), Amd1 (Mm), Amd1 (Rn)

Ensembl ID

ENSG00000123505 (Hs), ENSMUSG00000075232 (Mm), ENSRNOG00000000585 (Rn)

UniProtKB AC

P17707 (Hs), P31154 (Mm), P17708 (Rn)

EC number

4.1.1.50

Endogenous substrates

S-adenosyl methionine

Products

S-adenosyl-L-methioninamine

Cofactors

pyruvic acid

Selective inhibitors

sardomozide pIC₅₀ 8.0 [7]

Comment

S-allylglycine is also an inhibitor of SAMDC [4].

References

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1. Coleman CS, Hu G, Pegg AE. (2004) Putrescine biosynthesis in mammalian tissues. Biochem J, 379 (Pt 3): 849-55. [PMID:14763899]

2. Daidone F, Montioli R, Paiardini A, Cellini B, Macchiarulo A, Giardina G, Bossa F, Borri Voltattorni C. (2012) Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors. PLoS ONE, 7 (2): e31610. [PMID:22384042]

3. Garbarg M, Barbin G, Rodergas E, Schwartz JC. (1980) Inhibition of histamine synthesis in brain by alpha-fluoromethylhistidine, a new irreversible inhibitor: in vitro and in vivo studies. J Neurochem, 35 (5): 1045-52. [PMID:7452304]

4. Pajunen AE, Hietala OA, Baruch-Virransalo EL, Piha RS. (1979) The effect of DL-allylglycine on polyamine and GABA metabolism in mouse brain. J Neurochem, 32 (5): 1401-8. [PMID:438812]

5. Qu N, Ignatenko NA, Yamauchi P, Stringer DE, Levenson C, Shannon P, Perrin S, Gerner EW. (2003) Inhibition of human ornithine decarboxylase activity by enantiomers of difluoromethylornithine. Biochem J, 375 (Pt 2): 465-70. [PMID:12859253]

6. Saha AK, Schwarsin AJ, Roduit R, Masse F, Kaushik V, Tornheim K, Prentki M, Ruderman NB. (2000) Activation of malonyl-CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside. J Biol Chem, 275 (32): 24279-83. [PMID:10854420]

7. Stanek J, Caravatti G, Frei J, Furet P, Mett H, Schneider P, Regenass U. (1993) 4-Amidinoindan-1-one 2'-amidinohydrazone: a new potent and selective inhibitor of S-Adenosylmethionine decarboxylase. J Med Chem, 36 (15): 2168-71. [PMID:8340919]

8. Stanek J, Frei J, Mett H, Schneider P, Regenass U. (1992) 2-substituted 3-(aminooxy)propanamines as inhibitors of ornithine decarboxylase: synthesis and biological activity. J Med Chem, 35 (8): 1339-44. [PMID:1573631]

9. Wu JY, Matsuda T, Roberts E. (1973) Purification and characterization of glutamate decarboxylase from mouse brain. J Biol Chem, 248 (9): 3029-34. [PMID:4700449]

10. Zhu MY, Iyo A, Piletz JE, Regunathan S. (2004) Expression of human arginine decarboxylase, the biosynthetic enzyme for agmatine. Biochim Biophys Acta, 1670 (2): 156-64. [PMID:14738999]

How to cite this family page

Database page citation:

Decarboxylases. Accessed on 09/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=256.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.