What is ALAD gene?
The ALAD gene provides instructions for making an enzyme known as delta-aminolevulinate dehydratase. This enzyme is involved in the production of a molecule called heme. Heme is vital for all of the body’s organs, although it is found mostly in the blood, bone marrow, and liver.
What is ALAD deficiency porphyria mutation?
ALAD porphyria is a very rare genetic metabolic disease characterized by almost complete deficiency of the enzyme delta-aminolevulinic acid (ALA) dehydratase. Deficiency of this enzyme leads to the accumulation of the porphyrin precursor ALA, which can potentially result in a variety of symptoms.
How does lead inhibit ALAD?
Lead inhibits several enzymes in the heme synthesis, primarily ALAD (Figure 8). The ALAD inhibition can be restored to normal by addition of reduced glutathione or dithiothreitol in vitro.
What is Doss porphyria?
Aminolevulinic acid dehydratase deficiency porphyria (also known as “Doss porphyria”, “plumboporphyria”, or “ADP”) is a rare autosomal recessive metabolic disorder that results from inappropriately low levels of the enzyme delta-aminolevulinic acid dehydratase (ALAD), which is required for normal heme synthesis.
Which class of enzymes does Delta Ala synthase belong to?
proteobacteria
δ-aminolevulinic acid + CoA + CO. This enzyme is expressed in all non-plant eukaryotes and the α-class of proteobacteria and the reaction it catalyses is sometimes referred to as the Shemin pathway for ALA formation.
Is Ala a porphyrin?
Delta-aminolevulinic acid (ALA) dehydratase (ALAD) porphyria (ADP) is an acute porphyria resulting from severe ALAD deficiency that is caused by a genetic defect. The first two cases [1] and the fifth [2] were identified in Germany by Doss, and therefore the disease is referred to as Doss porphyria.
What are the symptoms of acute intermittent porphyria?
Signs and symptoms of acute porphyria may include:
- Severe abdominal pain.
- Pain in your chest, legs or back.
- Constipation or diarrhea.
- Nausea and vomiting.
- Muscle pain, tingling, numbness, weakness or paralysis.
- Red or brown urine.
- Mental changes, such as anxiety, confusion, hallucinations, disorientation or paranoia.
What causes erythropoietic Protoporphyria?
Erythropoietic protoporphyria (EPP) is a rare inherited metabolic disorder caused by a deficiency of the enzyme ferrochelatase (FECH), which results from changes (mutations) in the FECH gene.
How does lead effect heme synthesis?
Lead intoxication results in a disturbance of heme biosynthesis, its degree depending on the severity and duration of exposure to lead. A mild secondary, sideroblastic anemia is common; basophilic stippling may occur, especially in severe lead poisoning.
How does lead inhibit heme synthesis?
Lead Poisoning: Lead interacts with zinc cofactors for ALA dehydratase and ferrochelatase leading to inhibition of these two enzymes in the biochemical biosynthetic pathway of heme. This inhibition leads to mostly ALA and some protoporphyrin IX accumulating in urine.
What enzyme is deficient in porphyria?
Acute intermittent porphyria (AIP) is a rare metabolic disorder that is characterized by partial deficiency of the enzyme hydroxymethylbilane synthase (also known as porphobilinogen deaminase). This enzyme deficiency can result in the accumulation of porphyrin precursors in the body.
What is the effect of drugs on ALA synthase activity?
Thus, drugs and chemicals which induce cytochrome P450 apoproteins and at the same time inhibit enzymes of heme synthesis and/or accelerate heme breakdown cause the highest increases in ALA synthase activity.
