Influence of 1,10-phenanthroline and its analogues, other chelators and transition metal ions on dipeptidase activity of the rumen bacterium, Prevotella ruminicola.
Prevotella ruminicola plays a prominent role in the breakdown of peptides in the rumen, a process which contributes to excessive ammonia production and inefficient nitrogen retention in ruminants. Various metal ions and chelators were examined to assess how the metal ion-dependent dipeptidase activity of P. ruminicola M384 might be inhibited. Using sonicated extracts, Cu2+, Cr2+ and Hg2+ were most inhibitory, decreasing Ala2 breakdown to 15, 15 and 5% of control activity, whereas Co2+, Mn2+ and Zn2+ stimulated activity by 189, 30 and 26%, respectively. The chelators, EDTA, EGTA, TPEN and 1,10-phenanthroline, were inhibitory, as were several phenanthroline analogues. Among the stereoisomers of 1,10-phenanthroline tested, derivatives methylated on C-2 and C-9 were less effective than the parent molecule, but 3,4,7,8-tetramethyl-1,10-phenanthroline (TMP) was more inhibitory. Titration of the most effective inhibitors showed that EDTA, TPEN and TMP had similar potency and were effective at 0.1 mmol l-1 and above. Thus some metal ions and chelators are potent inhibitors of P. ruminicola dipeptidase, although they are unlikely to be sufficiently specific to peptide metabolism to be useful in vivo.
Wallace
R J
RJ
Rowett Research Institute, Bucksburn, Aberdeen, UK.
McKain
N
N
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D007477:Ions; D008670:Metals / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*; D018720:Prevotella / Q000187:drug effects / Q000201:enzymology*; D012417:Rumen / Q000382:microbiology; D012756:Sheep; D013329:Structure-Activity Relationship
D002614:Chelating Agents; D005029:Ethylenediamines; D007477:Ions; D008670:Metals; D010618:Phenanthrolines; D004533:Egtazic Acid; D004492:Edetic Acid; D004150:Dipeptidases; C038937:dipeptidase; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; C025205:1,10-phenanthroline