Porphyrias and Heme Biosynthesis Overview

<p>Uroporphyrinogen decarboxylase (D)</p> Signup and view all the answers

<p>Photosensitivity leading to itching and burning (C)</p> Signup and view all the answers

<p>Liver (D)</p> Signup and view all the answers

<p>Increase hepatic ALA synthase activity (A)</p> Signup and view all the answers

<p>Increases heme synthesis (B)</p> Signup and view all the answers

<p>Acute intermittent porphyria (B)</p> Signup and view all the answers

<p>Coproporphyrinogen III (A)</p> Signup and view all the answers

<p>Erythropoietic protoporphyria (A), Porphyria cutanea tarda (B), Variegate porphyria (D)</p> Signup and view all the answers

<p>Intravenous injection of hemin (C)</p> Signup and view all the answers

<p>Acute intermittent porphyria (B)</p> Signup and view all the answers

<p>Accumulation of toxic intermediates (D)</p> Signup and view all the answers

<p>Protoporphyrinogen IX accumulates in urine. (B)</p> Signup and view all the answers

<p>Congenital erythropoietic porphyria (A), Porphyria cutanea tarda (B), Erythropoietic protoporphyria (D)</p> Signup and view all the answers

Cyclic molecules composed of four linked pyrrole rings connected by methenyl bridges. They have various side chains attached to the pyrrole rings, determining their specific type.

A metalloporphyrin with iron (Fe²⁺) coordinated at its center. It is a prosthetic group vital for proteins like hemoglobin, myoglobin, and cytochromes.

The process of synthesizing heme, which occurs primarily in the liver and erythrocyte-producing cells of the bone marrow. It involves multiple enzymatic reactions, with the initial and final steps taking place in mitochondria.

Excessive production of heme leads to its accumulation and oxidation into hemin. Hemin then inhibits the activity of hepatic ALA synthase, a crucial enzyme in heme synthesis.

Drugs like phenobarbital, griseofulvin, and hydantoins increase the activity of hepatic ALA synthase, leading to enhanced heme production. This occurs because these drugs are metabolized by cytochrome P450 monooxygenase, requiring heme. Increased drug metabolism depletes heme, triggering the synthesis of more ALA synthase.

Genetic disorders characterized by deficiencies in heme synthesis, resulting in the accumulation and excretion of porphyrins or their precursors. They can be classified based on affected cells and their severity.

The most prevalent type of porphyria, characterized by a deficiency in uroporphyrinogen decarboxylase. It leads to the accumulation of uroporphyrin, which is excreted in the urine. It causes photosensitivity and reddish-brown urine.

Inherited defects in heme synthesis can lead to various porphyria types, with different enzyme deficiencies affecting specific tissues. They are characterized by accumulation of porphyrins or precursors, causing distinct clinical manifestations.

An autosomal dominant disorder caused by a deficiency in the enzyme hydroxymethylbilane synthase, leading to accumulation of δ-aminolevulinate (ALA) and porphobilinogen in urine.

An autosomal dominant disorder caused by a deficiency in the enzyme coproporphyrinogen oxidase, leading to accumulation of coproporphyrinogen III and preceding intermediates in urine.

An autosomal dominant disorder caused by a deficiency in the enzyme protoporphyrinogen oxidase, leading to accumulation of protoporphyrinogen IX and preceding intermediates in urine.

An autosomal recessive disorder caused by a deficiency in the enzyme ferrochelatase, leading to accumulation of protoporphyrin IX in erythrocytes, bone marrow, and plasma.

An autosomal recessive disorder caused by a deficiency in the enzyme uroporphyrinogen III synthase, leading to accumulation of uroporphyrinogen I and coproporphyrinogen I in urine.

The enzyme responsible for the first step in heme synthesis, which is upregulated in porphyrias due to the lack of heme feedback inhibition.

The treatment approach for porphyrias includes managing symptoms like pain and vomiting, reducing the synthesis of porphyrin precursors with hemin administration, protecting from sunlight exposure, and using free radical scavengers.