The enzymic condensation of porphobilinogen to porphyrins

Abstract

is no correlation between anticholinesterase activity and effectiveness as reactivator. The ratios (potency as reactivator:reactivity with organophosphates), obtained with different oximes, support the interpretation that attachment to the phosphorylated enzyme during reactivation enhances activity. Possible sites of attachment are discussed. We wish to thank the Department of Scientific and Industrial Research for the special research grant to P. W.S., which has defrayed some of the cost of this work. We are also grateful to Miss M. E. Williams for her help.

Studies on the porphobilinogen deaminase–uroporphyrinogen cosynthetase system of cultured soya-bean cells

“…Preheating of the porphobilinogenase at 700C for 30min destroyed isomerase activity almost completely, resulting in an increase of total uroporphyrin formation (Table 4). These results agree with the findings of Booij & Rimington (1957), Lockwood & Benson (1960), Cornford (1964) and Llambias & Batlle (1970d). Heat inactivation is slightly greater, occurring after shorter time-intervals, when isomerase is heated alone.…”

“…It has also been found that 8-aminolaevulate dehydratase, isolated from the same tissue, was firmly bound to a nucleoprotein (Tigier et al 1970). Bogorad (1958a,b), Lockwood & Benson (1960) and Sancovich et al (1969b) have shown that porphobilinogenase and deaminase were as active in the absence of oxygen as in its presence; we have observed that the activity of porphobilinogenase was affected by the presence of air. The yield of uroporphyrinogens was highest under anaerobic conditions, although consumption of substrate was not modified by air, suggesting that some intermediate in the reaction was still being formed, but that this compound, probably some polypyrrolic intermediate (Llambias & Batlle, 1970a), must be in the reduced form to be further enzymically converted into uroporphyrinogens; the presence of air would prevent this reduction (A. M. Stella, V. E. Parera, E. B. C. Llambfas & A. M. del C. Batlle, unpublished work).…”

“…The stability of the deaminase was found to be the same as that of the whole system. As has been shown in other tissues (Booij & Rimington, 1957;Lockwood & Rimington, 1957;Bogorad, 1958a,b;Granick & Mauzerall, 1958;Lockwood & Benson, 1960;Cornford, 1964;Sancovich et al 1969a,b), soya-bean callus isomerase is also a heat-labile enzyme. Preheating of the porphobilinogenase at 700C for 30min destroyed isomerase activity almost completely, resulting in an increase of total uroporphyrin formation (Table 4).…”

“…It has also been found that the soya-bean callus enzymes have kinetic behaviour and parameters very different from those of the same enzymes obtained from other sources (Lockwood & Benson, 1960;Sancovich et al 1969b;Llambias & Batlle, 1970b,c).…”

“…A part of the pathway that has stimulated much speculation is the step involving the condensation of porphobilinogen to uroporphyrinogens. It has been known since 1953 that porphobilinogen is an intermediate in the biosynthesis of porphyrins (Falk, Dresel & Rimington, 1953;Bogorad & Granick, 1953) and a good deal of information is available on the enzyme system concerned, whioh is widely distributed (Lockwood & Rimington, 1957;Bogorad, 1958a,b;Granick & Mauzerall, 1958;Heath & Hoare, 1959a,b;Lockwood & Benson, 1960;Levin & Coleman, 1967;Stevens, Frydman & Frydman, 1968; Levin, 1968;Sancovich, Batlle & Grinstein, 1969a,b),…”