A 10-year old boy presented with muscle weakness and fatigue with increased lead in the blood. Which of the following enzyme production in the liver is increased?
Ans. a. ALA synthase (Ref Harper 28/ e p272,278. 563)High levels of lead can affect heme metabolism by combining with SH groups in enzymes such as Ferrocheiatase and ALA dehydratase (zinc containing enzyme). This affects porphyrin metabolism. Elevated levels of protoporphyrin are found in red blood cells and elevated levels of ALA and Coproporphyrin are found in urine. It appears that heme, probably acting through an aporepressor molecule, acts as a negative regulator of the synthesis of ALA synthase. Thus, the rate of synthesis of ALA synthase increases greatly in the absence of heme and is diminished in its presence."ALA synthase occurs in both hepatic (ALASI) and erythroid (ALAS2) forms. The rate-limiting reaction in the synthesis of heme in liver is that catalyzed by ALAS1, a regulatory enzyme. It appears that heme, probably acting through an aporepressor molecule, acts as a negative regulator of the synthesis of.ALASI Thus, the rate of synthesis of ALASl increases greatly in the absence of heme and is diminished in its presence. "-Harper 28/e p563
ALA synthase
Heme oxygenase
Ferrochelatase
Porphobilinogen deaminase
Enzymes