Inhibition of porphobilinogen synthase (PBG-synthase) by 4,6-dioxoheptanoic acid (1) and related compounds

Data

The tested compounds are listed bellow with the determined Michaelis constant K_m, inhibition constant K_i and inhibition type.

	Compounds	K_m [µM]	K_i [µM]	Type of inhibition and Remarks
1		70	1.4	Uncompetitive
2		62	319	Uncompetitive
3		44	14.5	Uncompetitive
4		61	16.4	Competitive
5		61	337	Uncompetitive
6		61	28'000	Competitive
7		60	44'000	Mixed
8		60	5'520	Uncompetitive
9		54	328	Uncompetitive
10		43	15'000	Competitive
11		76	3'680	Uncompetitive
12		39	39'500	Competitive
13		45	X	No inhibitor
14		45	24'900	Uncompetitive
15		--	--	Hydrolyses in the testing conditions! K_i value larger than compound 2
16		--	--	Hydrolyses in the testing conditions! K_i value larger than compound 2
17		--	--	Slow-binding
18		--	--	Formation of pyrrole with 5-aminlevulinic acid. Not possible to test!
19		--	--	UV absorption in the range used for the pyrrole formation determination
20		--	--	UV absorption in the range used for the pyrrole formation determination

All the compounds are drawn in their diketo form. In solution they are present as a mixture of the keto and the enol form. The following table gives the percentage of the enol form present in CDCl3 as determined by 1H-NMR. The determinations of the enol content were performed using concentrations comprised between 5 and 20 mM.

compounds	1	2	3	4	5	8	9	10	11
Enol %	90	71	81	97	90	61	98	41	85

Continue

Go to presentation page