Description
Diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) inhibits heme production by inhibiting ferrochelatase, the enzyme that catalyzes the addition of Fe
2+ to protoporphyrin IX to create heme B. Chronic DDC administration induces Mallory-Denk body formation, a feature of alcoholic and non-alcoholic hepatitis, and reduces IL-12A methylation in mouse liver.
Chemical Properties
almost white crystalline powder
Uses
Diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate was used to induce Mallory-Denk body formation in mice
in vivo.
Definition
ChEBI: A dihydropyridine that is 2,4,6-trimethyl-1,4-dihydropyridine substituted by ethoxycarbonyl groups at positions 3 and 5.
Biochem/physiol Actions
Diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate blocks the heme synthesis and prevents the induction of hepatic heme oxygenase-1 in mice.
Purification Methods
Crystallise the ester from hot EtOH/water mixture. [Beilstein 22 H 147, 22 I 529, 22 II 100, 22 III/IV 1594.]
References
[1] J. ONISAWA R L. Effects of diethyl-1, 4-dihydro-2, 4,6-trimethylpyridine-3,5-dicarboxylate on the metabolism of porphyrins and iron.[J]. The Journal of Biological Chemistry, 1963, 44 1: 724-727. DOI:
10.1016/s0021-9258(18)81326-6[2] QX YUAN. Mallory body induction in drug-primed mouse liver[J]. Hepatology, 1996, 24 3: Pages 603-612. DOI:
10.1053/jhep.1996.v24.pm0008781332[3] J. OLIVA S. W F. Changes in IL12A methylation pattern in livers from mice fed DDC[J]. Experimental and molecular pathology, 2012, 92 2: Pages 191-193. DOI:
10.1016/j.yexmp.2012.01.001
