Decarboxylases (E.C. 4.1.1.-)

Overview: The decarboxylases generate CO₂ and the indicated products from acidic substrates, requiring pyridoxal phosphate (ADC, AADC, GAD, HDC, ODC and PSDC) or pyruvate (SAMDC and PSDC) as a co-factor.

Nomenclature	S-Adenosylmethionine decarboxylase	L-Arginine decarboxylase	L-Aromatic amino-acid decarboxylase	Glutamic acid decarboxylase
E.C.	4.1.1.50	4.1.1.19	4.1.1.28	4.1.1.15
Preferred abbreviation	SAMDC	ADC	AADC	GAD
Other names	–	Ornithine decarboxylase- like protein (Zhu et al., 2004)	DOPA decarboxylase (DDC), 5-hydroxytryptophan decarboxylase	GAD1 (GAD65), GAD2 (GAD67)
Ensembl ID	ENSG00000123505	ENSG00000142920	ENSG00000132437	ENSG00000128683, ENSG00000136750
Substrate(s)	S-Adenosylmethionine	L-Arginine	DOPA, L-tryptophan, 5-hydroxy-L-tryptophan	L-Glutamate, L-aspartate
Product(s)	5′-Deoxyadenosyl-(3-aminopropyl) methylsulfonium	Agmatine	5-Hydroxytryptophan, dopamine	GABA
Selective inhibitors	SAM486A (8.0; Stanek et al., 1993), AMA	–	Benserazide, carbidopa, 3-hydroxybenzylhydrazine, L-α-methyldopa	S-Allylglycine

The presence of a functional ADC activity in human tissues has been questioned (Coleman et al., 2004). s-Allylglycine is also an inhibitor of SAMDC (Pajunen et al., 1979).

Nomenclature	Histidine decarboxylase	Malonyl-CoA decarboxylase	Ornithine decarboxylase	Phosphatidylserine decarboxylase
E.C.	4.1.1.22	4.1.1.9	4.1.1.17	4.1.1.65
Preferred abbreviation	HDC	MLYCD	ODC	PSDC
Ensembl ID	ENSG00000140287	ENSG00000103150	ENSG00000115758	ENSG00000100141
Substrate(s)	L-Histidine	Malonyl-CoA	L-Ornithine	Phosphatidylserine
Product	Histamine	Acetyl-CoA	Putrescine	Phosphatidylethanolamine
Endogenous regulation	–	AMP-activated protein kinase-evoked phosphorylation (Saha et al., 2000)	Antizymes (ENSG00000104904, ENSG00000180304, ENSG00000143450), which tonically inhibit IDC activity Antizyme inhibitor (ENSG00000155096)	–
Selective inhibitors	α-Fluoromethylhistidine (Garbarg et al., 1980)		Eflornithine, 1-aminooxy-3-aminopropane	–

Glossary

Abbreviations:

AMA

S-(5′-deoxy-5′-adenosyl)-methylthioethyl-hydroxylamine

SAM

S-adenosylmethionine

SAM486A

1-guanidinoimino-2,3-dihydroindene-4-carboximidamide, also known as CGP48664

Further Reading

Ai W, Takaishi S, Wang TC, Fleming JV (2006). Regulation of L-histidine decarboxylase and its role in carcinogenesis. Prog Nucleic Acid Res Mol Biol81: 231–270.

Akbarian S, Huang HS (2006). Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders. Brain Res Rev52: 293–304.

Bouzakri K, Austin R, Rune A et al. (2008). Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle. Diabetes57: 1508–1516.

Moya-Garcia AA, Pino-Angeles A, Gil-Redondo R, Morreale A, Sanchez-Jimenez F (2009). Structural features of mammalian histidine decarboxylase reveal the basis for specific inhibition. Br J Pharmacol157: 4–13.

Pegg AE (2006). Regulation of ornithine decarboxylase. J Biol Chem281: 14529–14532.

Smith KJ, Skelton H (2006). α-Difluoromethylornithine, a polyamine inhibitor: its potential role in controlling hair growth and in cancer treatment and chemo-prevention. Int J Dermatol45: 337–344.

Wei J, Wu JY (2008). Post-translational regulation of L-glutamic acid decarboxylase in the brain. Neurochem Res33: 1459–1465.