RESUMO
A novel hydroxymethylbilane analog, 19-Br-HMB (11), has been synthesized. Its activity with the enzyme Uro'gen III synthase shows competitive inhibition.
Assuntos
Uroporfirinogênio III Sintetase/antagonistas & inibidores , Uroporfirinogênios/farmacologia , Ligação Competitiva , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Uroporfirinogênios/biossíntese , Uroporfirinogênios/síntese química , Uroporfirinogênios/químicaRESUMO
Insights into details of the biomechanism by which porphobilinogen (1) cyclotetramerizes to uroporphyrinogen III (2) as well as promising synthetic applications are provided by investigation of this reaction in vitro. The cyclotetramerization of newly prepared norporphobilinogen (5) proved to be extemely specific due to strong conformation control. Advantage was taken of this finding by preparing a N,N,N,N-tetramethyl-porphyrinogen (13a) for the first time. Protected derivatives of the linear tetramer of porphobilinogen (20c) which is regarded as an intermediate of the cyclotetramerization were gained by total synthesis and their transformations investigated.
Assuntos
Porfobilinogênio/metabolismo , Porfirinogênios/biossíntese , Uroporfirinogênios/biossíntese , Porfobilinogênio/análogos & derivados , Uroporfirinogênios/síntese químicaRESUMO
The preparation of the aminomethyl-bilinogen which results from formal "head to tail" condensation of porphobilinogen is described. The chemical cyclocondensation of this compound at pH 7.4 yields uroporphyrinogen I. Enzymatic studies with enzyme preparations from Propionibacterium shermanii, which synthesize uroporphyrinogens from porphobilinogen, show that the rate of cyclisation is increased by these enzymes and indicate that the bilinogen also might be used for uroporphyrinogen III formation. This is also suggested by studies on the formation of cobyrinic acid from [4-14C]5-aminolevulinate via uroporphyrinogen III in the presence of the aminomethylbilinogen by cell-free extracts from Clostridium tetanomorphum.