Step I porphria doubts

[voicesinmyhead]

a) In acute intermittent porphyria, why is there an increase in urinary uroporphyrin, considering uroporphyrins come below the enzyme block (PBG deaminase)?

b) how does low calorie diet, alcohol and enzyme inducing drugs lead to low heme in the liver? (which then lead to porphyria)?

 

[Mleechu]

B - P450 are heme containing enzymes and induction(^levels) of these enzyme leads to accelerated heme consumption.

 

[Transposony]

a) In acute intermittent porphyria, why is there an increase in urinary uroporphyrin, considering uroporphyrins come below the enzyme block (PBG deaminase)?

b) how does low calorie diet, alcohol and enzyme inducing drugs lead to low heme in the liver? (which then lead to porphyria)?

a) Are you sure you are reading it right? It's Porphyria cutanea tarda which causes an increase in urinary Uroporphyrin.
Acute intermittent porphyria causes an increase in urinary porphobilinogen.

b) The classic inducers of porphyria are chemicals or situations that boost heme synthesis. This includes fasting and drugs.
In general, drugs that lead to increased activity of the hepatic P450 system, such as phenobarbital, sulfonamides, estrogens, and alcohol, are associated with porphyria.
Cytochromes P450 (CYPs) belong to the superfamily of proteins containing a heme cofactor. In response to these drugs, the synthesis of CYP proteins increases (need more enzymes to metabolize these drugs), leading to an increased consumption of heme (since heme is a co-factor for cytochromes P450) causing a decrease in heme concentration in liver. The decrease in heme concentration also activates ALA synthase making things worse.

 

[voicesinmyhead]

a) Are you sure you are reading it right? It's Porphyria cutanea tarda which causes an increase in urinary Uroporphyrin.
Acute intermittent porphyria causes an increase in urinary porphobilinogen.

b) The classic inducers of porphyria are chemicals or situations that boost heme synthesis. This includes fasting and drugs.
In general, drugs that lead to increased activity of the hepatic P450 system, such as phenobarbital, sulfonamides, estrogens, and alcohol, are associated with porphyria.
Cytochromes P450 (CYPs) belong to the superfamily of proteins containing a heme cofactor. In response to these drugs, the synthesis of CYP proteins increases (need more enzymes to metabolize these drugs), leading to an increased consumption of heme (since heme is a co-factor for cytochromes P450) causing a decrease in heme concentration in liver. The decrease in heme concentration also activates ALA synthase making things worse.

awesome explanation thanks! and the first doubt was an error in the old FA. sorry about that!

 

[Brucelaa67]

a) Are you sure you are reading it right? It's Porphyria cutanea tarda which causes an increase in urinary Uroporphyrin.
Acute intermittent porphyria causes an increase in urinary porphobilinogen.

b) The classic inducers of porphyria are chemicals or situations that boost heme synthesis. This includes fasting and drugs.
In general, drugs that lead to increased activity of the hepatic P450 system, such as phenobarbital, sulfonamides, estrogens, and alcohol, are associated with porphyria.
Cytochromes P450 (CYPs) belong to the superfamily of proteins containing a heme cofactor. In response to these drugs, the synthesis of CYP proteins increases (need more enzymes to metabolize these drugs), leading to an increased consumption of heme (since heme is a co-factor for cytochromes P450) causing a decrease in heme concentration in liver. The decrease in heme concentration also activates ALA synthase making things worse.

I know this is an old post, but I hope it can resolve a doubt.
Sulfonamides are given under CYP-450 inhibitors (FA 2017). So why/how does it precipitate porphyria?