Control of the rate of heme synthesis in liver cells is achieved largely through regulation of which enzyme?

• A. ALA synthase
• B. ALA dehydratase
• C. PBG deaminase
• D. Ferrochelatase

Answer: (A)

The rate of heme production in liver cells is governed mainly by the first enzyme in the pathway, ALA synthase. This enzyme catalyzes the condensation of glycine and succinyl-CoA to form delta-aminolevulinic acid, the initial step that gates the entire downstream sequence. Because it is the rate-limiting step, its activity sets how fast the whole pathway can proceed.

In liver tissue, ALA synthase (the ALAS1 isoform) is tightly controlled by feedback from heme itself: when heme levels are high, ALAS1 activity and expression are suppressed, slowing synthesis; when heme is low, this inhibition is relieved and the pathway speeds up. This negative feedback ensures balance between heme production and the cell’s needs.

The other enzymes listed act later in the pathway, so they do not determine the overall rate of synthesis under normal conditions.