Alcohol-Induced Decrease in Uroporphyrinogen Decarboxylase Activity in Rat Liver and Spleen

Enzyme ◽  
1981 ◽  
Vol 26 (1) ◽  
pp. 24-31 ◽  
Author(s):  
M. Doss ◽  
R. von Tiepermann ◽  
G. Stutz ◽  
R. Teschke
Keyword(s):  
Rat Liver ◽  
Decarboxylase Activity ◽  
Uroporphyrinogen Decarboxylase

scholarly journals Investigations of rat liver uroporphyrinogen decarboxylase. Comparisons of porphyrinogens I and III as substrates and the inhibition by porphyrins

1981 ◽  
Vol 195 (1) ◽  
pp. 241-250 ◽  
Author(s):  
A G Smith ◽  
J E Francis
Keyword(s):  
Rat Liver ◽  
Rapid Analysis ◽  
Oxidation Products ◽  
Decarboxylase Activity ◽  
Effective Inhibitor ◽  
Uroporphyrinogen Decarboxylase ◽  
The Difference ◽  
Substrate Concentrations ◽  
Slow Turnover

1. The decarboxylations of uroporphyrinogens, hepta-, hexa- and penta-carboxyporphyrinogens I and III by porphyrinogen carboxy-lyase (EC 4.1.1.37) in rat liver supernatant have been compared as functions of substrate concentrations. Although Km and Vmax. (for total porphyrinogens formed) were estimated, prophyrinogens and CO2 produced at 1 microM were considered to be a better indication of real relative rates, owing to substrate/product inhibitions. Uroporphyrinogen III was the best substrate by the criteria of Km/Vmax. and decarboxylation at 1 microM and was converted into coproporphyrinogen more quickly than its series-I isomer. 2. The difference between uroporphyrinogens I and III as substrates was confirmed by using a mixture of [14C8]uroporphyrinogens, the discrimination occurring principally in the first decarboxylation. 3. Porphyrins, especially oxidation products of the substrates, inhibited the enzyme. Heptacarboxyporphyrin III was the most effective inhibitor of both uroporphyrinogen III and heptacarboxyporphyrinogen III conversion into coproporphyrinogen. 4. Rapid analysis of the livers from rats made porphyric with hexachlorobenzene demonstrated that substantial quantities of the tetrapyrroles were present in vivo as the porphyrinogens (21-42%). 5. Enzymic decarboxylation of uroporphyrinogen III in 2H2O-containing buffer gave [2H4]coproporphyrinogen. 6. Rats treated with cycloheximide for 10h showed no decrease in uroporphyrinogen decarboxylase activity/mg of protein, suggesting a relatively slow turnover of the enzyme.

The Effect of the Porphyrogenic Compound, Hexachlorobenzene, on the Activity of Hepatic Uroporphyrinogen Decarboxylase in the Rat

1976 ◽  
Vol 51 (1) ◽  
pp. 71-80 ◽  
Author(s):  
G. H. Elder ◽  
J. O. Evans ◽  
S. A. Matlin
Keyword(s):  
Rat Liver ◽  
Wistar Rats ◽  
New Method ◽  
Decarboxylase Activity ◽  
Uroporphyrinogen Decarboxylase ◽  
Enzyme Defect ◽  
Female Wistar Rats ◽  
Liver Homogenates

1. A new method for the measurement of uroporphyrinogen decarboxylase (EC 4.1.1.37) in rat liver homogenates, with 5-carboxyl porphyrinogen as substrate, is described. 2. The administration of a diet containing 0·3% (w/w) hexachlorobenzene produces porphyria in female Wistar rats after a delay of at least 4 weeks. The development of porphyria is accompanied by a progressive fall in hepatic uroporphyrinogen decarboxylase activity to 18% of control values after 11 weeks. The features of hexachlorobenzene porphyria are consequences of this enzyme defect. 3. Feeding with hexachlorobenzene did not lead to the accumulation of iron in the liver. It is suggested that hexachlorobenzene or a metabolite acts directly to decrease the activity of the enzyme.

Effects of Hexachlorobenzene Feeding and Iron Overload on Enzymes of Haem Biosynthesis and Cytochrome P450 in Rat Liver

1977 ◽  
Vol 53 (2) ◽  
pp. 111-115 ◽  
Author(s):  
M. Louw ◽  
A. C. Neethling ◽  
V. A. Percy ◽  
M. Carstens ◽  
B. C. Shanley
Keyword(s):  
Cytochrome P450 ◽  
Synergistic Effect ◽  
Progressive Increase ◽  
Decarboxylase Activity ◽  
Progressive Decrease ◽  
Uroporphyrinogen Decarboxylase ◽  
Time Intervals ◽  
Liver Cytochrome ◽  
Haem Biosynthesis ◽  
P450 Concentration

1. The effect of hexachlorobenzene feeding on liver δ-aminolaevulinate synthase, uroporphyrinogen decarboxylase and cytochrome P450 was studied at various time-intervals in siderotic and non-siderotic rats. 2. In the non-siderotic group hexachlorobenzene feeding led to a progressive decrease in liver uroporphyrinogen decarboxylase activity, accompanied by a progressive increase in δ-aminolaevulinate synthase activity. Cytochrome P450 concentrations were above normal throughout but fell toward the end of the experiment. 3. Similar but more marked changes were found in the siderotic animals. The fall in uroporphyrinogen decarboxylase activity occurred earlier and was significantly greater in these animals, whereas the increase in δ-aminolaevulinate synthase activity was consistently larger. Liver cytochrome P450 concentration also rose but to a lesser extent than that in the non-siderotic rats. 4. Hexachlorobenzene-induced porphyria would seem to be attributable to inhibition or inactivation of hepatic uroporphyrinogen decarboxylase. Hepatic siderosis has a synergistic effect with hexachlorobenzene on this enzyme and may exert additional effects by promoting cytochrome P450 turnover.

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