Inhibiting ALA synthase

[zhopv10]

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Does anyone happen to know the mechanism behind why hemin and glucose inhibit delta ALA synthase?

 

[Entadus]

Had never heard of Hemin, but I'm guessing its porphyrin structure (looks like Heme) makes it structurally similar enough to bind ALA-S (mimics the endogenous substrate)

Hematin and heme arginate are the drugs of choice in acute porphyria, in the United States and the United Kingdom, respectively. These drugs need to be given very early in an attack to be effective. Effectiveness varies among individuals. They are not curative drugs, but can shorten attacks and reduce the intensity of an attack. Side-effects are rare but can be serious. These heme-like substances, in theory, inhibit ALA synthase and, hence, the accumulation of toxic precursors.

-Wikipedia

Glucose I've no idea.

 

[tasar1898]

I guess both are allosteric inhibitors of the ALAsynthase.. Heme/heme-like molecules make sense as neg-feedback of the biosynthesis pathway.. Glucose maybe inhibits because the synthesis is more efficient during the fasting state ?? I just memorized that

 

[stop2stop]

Yeah the glucose point is interesting and one I've wondered about as well. Heme obviously makes sense. Could it be sort of the reverse of pyruvate carboxylase being active only when we have ATP around, perhaps related here to gluconeogenesis as well and needing energy for that instead? Trying to wrap my head around it, still not sure

 

[zhopv10]

Thanks guys! Ya I was figuring the heme part as negative feedback as well (according to firecracker hemin is 3+ iron which makes less sense to me than the hematin which I've heard more of.) But ya that glucose... I was figuring it had to be something with the TCA since glycine and succinyl coa are the starting points for ALA but ya idk...

Ah well, I'll just memorize it for now and if I get ambitious enough maybe I'll looking for it. Haha