Why Glucose for AIP?

[BloodySurgeon]

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How does glucose inhibit ALA synthase for AIP?

 

[lemonade90]

Has to deal with transcription.

"About 15% of heme production occurs the liver. Hepatocyte heme production must be controlled to respond to changing metabolic requirements. Hepatocytes express ALAS-1, a 'housekeeping' form of ALAS. Increasing heme levels create a negative feedback that downregulate transcription of ALAS-1 and inhibit its import into the mitochondrial matrix. ALAS-1 transcription is upregulated by peroxisome proliferator-activated receptor coactivator 1 (PGC-1). Transcription of PGC-1 is regulated by glucose levels. Hypoglycemia induces PGC-1 production, increasing ALAS-1 and heme synthesis. This promotes the clinical appearance of the acute porphyrias."

From: http://library.tcmedc.org/webpath/hemehtml/heme243.htm

So hyperglycemia-->decreased PGC-1 production-->decreased ALAS1-->decreased heme synthesis. This of course is what you would want to prevent build of intermediates.

 

[Phloston]

Has to deal with transcription.

"About 15% of heme production occurs the liver. Hepatocyte heme production must be controlled to respond to changing metabolic requirements. Hepatocytes express ALAS-1, a 'housekeeping' form of ALAS. Increasing heme levels create a negative feedback that downregulate transcription of ALAS-1 and inhibit its import into the mitochondrial matrix. ALAS-1 transcription is upregulated by peroxisome proliferator-activated receptor coactivator 1 (PGC-1). Transcription of PGC-1 is regulated by glucose levels. Hypoglycemia induces PGC-1 production, increasing ALAS-1 and heme synthesis. This promotes the clinical appearance of the acute porphyrias."

From: http://library.tcmedc.org/webpath/hemehtml/heme243.htm

So hyperglycemia-->decreased PGC-1 production-->decreased ALAS1-->decreased heme synthesis. This of course is what you would want to prevent build of intermediates.

I wonder if that has to do with the cAMP level, the same way it is with the lac-operon (i.e. cAMP is high with low glucose, enabling CRP binding, leading to RNA polymerase II binding).

 

[lemonade90]

I wonder if that has to do with the cAMP level, the same way it is with the lac-operon (i.e. cAMP is high with low glucose, enabling CRP binding, leading to RNA polymerase II binding).

Could be, but then the CRP should be in the cytosol because cAMP is a polar molecule. Prokaryotes have the luxury of not having nuclear membranes.