LCaI – Kinetic Mechanisms of Enzyme Inhibition and Activation

Linear catalytic inhibition

**Fingerprints of LCaI: Dependence of the parameters on [X]**

**Fingerprints of LCaI: Specific velocity plot and replot**

Featured examples

#	Enzyme Species	EC no.	Modifier	Substrate⁽¹⁾	Name given by authors⁽²⁾	Reference ⁽³⁾
1	Catechol 1,2-dioxygenase Acinetobacter baylyi	1.13.11.4 ⁽⁴⁾	4-Chlorocatechol	4-Chloroaniline	Uncompetitive inhibition K_X = 115 μM	Hongsawat (2011)
2	3-Oxo-5alpha-steroid 4-dehydrogenase (NADP+) Rattus norvegicus	1.3.1.22	Aryl steroid 1	Testosterone	Linear uncompetitive inhibition K_X = 88 nM	Brandt (1990) ⁽⁵⁾
3	3-Oxo-5alpha-steroid 4-dehydrogenase (NADP+) Rattus norvegicus	1.3.1.22	Aryl steroid 1	NADP_red	Linear uncompetitive inhibition K_X = 172 nM	Brandt (1990) ⁽⁵⁾
4	3-Oxo-5alpha-steroid 4-dehydrogenase (NADP+) Rattus norvegicus	1.3.1.22	Aryl steroid 2	Testosterone	Linear uncompetitive inhibition K_X = 53 nM	Brandt (1990) ⁽⁵⁾
5	3-Oxo-5alpha-steroid 4-dehydrogenase (NADP+) Rattus norvegicus	1.3.1.22	Aryl steroid 2	NADP_red	Linear uncompetitive inhibition K_X = 111 nM	Brandt (1990) ⁽⁵⁾
6	Inositol-phosphate phosphatase Bos taurus	3.1.3.25	Li⁺	Racemic myo-inositol 1-phosphate	Linear uncompetitive inhibition ⁽⁶⁾ K_X = 11.1 mM	Leech (1993)
7	Inositol-phosphate phosphatase Bos taurus	3.1.3.25	Li⁺	myo-Inositol 4-phosphate	Linear uncompetitive inhibition ⁽⁶⁾ K_X = 0.11 mM	Leech (1993)
8	Inositol-phosphate phosphatase Bos taurus	3.1.3.25	Li⁺	Adenosine-2'-phosphate	Linear uncompetitive inhibition ⁽⁶⁾ K_X = 1.52 mM	Leech (1993)
9	Alkaline phosphatase Homo sapiens	3.1.3.1	L-Tryptophan	Phenyl phosphate	Uncompetitive inhibition K_X = 0.6 mM (37°C)	Lin (1971)
10	Gamma-glutamyltransferase Homo sapiens	2.3.2.2	OU749	L-glutamic acid-γ-4-nitroanilide Transpeptidase reaction ⁽⁷⁾	Uncompetitive inhibition K_X = 73.8 μM	King (2009)
11	Gamma-glutamyltransferase Homo sapiens	2.3.2.2	OU749	D-glutamic acid-γ-4-nitroanilide Hydrolysis reaction	Uncompetitive inhibition K_X = 73 μM	Wickham (2012)
12	Gamma-glutamyltransferase Homo sapiens	2.3.2.2	Sodium benzosulfonamide	L-glutamic acid-γ-4-nitroanilide Transpeptidase reaction ⁽⁷⁾	Uncompetitive inhibition K_X = 28.8 mM	Wickham (2012)
13	Gamma-glutamyltransferase Homo sapiens	2.3.2.2	Sodium benzosulfonamide	D-glutamic acid-γ-4-nitroanilide Hydrolysis reaction	Uncompetitive inhibition K_X = 160 mM	Wickham (2012)
14	Tyrosinase Agaricus bisporus	1.14.18.1	[1,4’] Bipiperidinyl-1’-yl-naphthan-2-yl- methanone	4-[(4-methylbenzo)azo]-1,2- benzendiol	Uncompetitive inhibition K_X = 5.9 μM	Karbassi (2004)
15	beta-Galactosidase Escherichia coli	3.2.1.23	Glycofullerene 14 ⁽⁸⁾	p-Nitrophenyl β-D-Galactopyranoside	Uncompetitive inhibition K_X = 3.2 μM	Abellán Flos (2016)

⁽¹⁾ Always the varied substrate. In two- or more-substrate reactions the concentration(s) of the non varied substrate(s) is/are kept constant.

⁽²⁾ Name of the mechanism given by the authors in the quoted reference. α, β and the inhibition/activation constants for the modifier (X), uniformly denoted K_X, are the values specified by the authors. In some cases, missing parameters have been calculated from graphical or tabular data provided in the papers. In two- or more-substrate reactions, K_X represents an apparent constant at given concentrations of the fixed substrates and no calculations of the intrinsic values have been attempted.

⁽³⁾ Full references at the end of the page provide also the digital object identifier (doi), if available. Clicking the authors (highlighted) opens the reference in PubMed.

⁽⁴⁾ And related enzymes in the bacterial culture.

⁽⁵⁾ Measurements performed with rat liver microsomes. Double-inhibition analyses revealed cooperative binding between NADP_ox and aryl steroid 1 or aryl steroid 2.

⁽⁶⁾ Up to a concentration of 1.1 mM.

⁽⁷⁾ Transpeptidation reaction of gamma-glutamyltransferase: (5-L-glutamyl)-peptide + amino acid = peptide + 5-L-glutamyl amino acid. See also LSpI.

⁽⁸⁾ Complex structure: see Abellán Flos et al. (2016), Supplementary Information, p. 27.

References

Abellán Flos M, García Moreno MI, Ortiz Mellet C, García Fernández JM, Nierengarten J-F, Vincent SP (2016) Potent glycosidase inhibition with heterovalent fullerenes: Unveiling the binding modes triggering multivalent inhibition. Chem Eur J 22: 11450-11460. doi:10.1002/chem.201601673
Brandt M, Greway AT, Holt DA, Metcalf BW, Levy MA (1990) Studies on the mechanism of steroid 5-a-reductase inhibition by 3-carboxy A-ring aryl steroids. J Steroid Biochem Mol Biol 37: 575-579. doi:10.1016/0960-0760(90)90403-8
Hongsawat P, Vangnai AS (2011) Biodegradation pathways of chloroanilines by Acinetobacter baylyi strain GFJ2. J Hazard Mater 186: 1300-1307. doi:10.1016/j.jhazmat.2010.12.002
Karbassi F, Saboury AA, Hassan Khan MT, Choudhary MI, Saifi ZS (2004) Mushroom tyrosinase inhibition by two potent uncompetitive inhibitors. J Enzyme Inhib Med Chem 19: 349-353. doi:10.1080/14756360409162449
King JB, West MB, Cook PF, Hanigan MH (2009) A novel, species-specific class of uncompetitive inhibitors of gamma-glutamyl transpeptidase. J Biol Chem 284: 9059-9065. doi:10.1074/jbc.M809608200
Leech AP, Baker GR, Shute JK, Cohen MA, Gani D (1993) Chemical and kinetic mechanism of the inositol monophosphatase reaction and its inhibition by Li+. Eur J Biochem 212: 693-704. doi:10.1111/j.1432-1033.1993.tb17707.x
Lin CW, Sie HG, Fishman WH (1971) L-Tryptophan. A non-allosteric organ-specific uncompetitive inhibitor of human placental alkaline phosphatase. Biochem J 124: 509-516. doi:10.1042/bj1240509
Wickham S, Regan N, West MB, Kumar VP, Thai J, Li PK, Cook PF, Hanigan MH (2012) Divergent effects of compounds on the hydrolysis and transpeptidation reactions of γ-glutamyl transpeptidase. J Enzyme Inhib Med Chem 27: 476-489. doi:10.3109/14756366.2011.597748