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Heme Metabolism (1).pptx
- 1. Dr Himani
- 4. Haemoglobin
- 6. Heme • Heme is a member of a family of compounds called porphyrins. • Many important proteins contain heme as a prosthetic group.
- 7. Porphyrins • Porphyrins are cyclic compounds composed of held together by methenyl bridges.
- 8. Porphyrins • Porphyrins are substituted at positions 1-8
- 9. •Porphyrins
- 10. •Porphyrins
- 11. •Heme synthesis
- 12. •Heme synthesis - site Tissues •Liver •Bone marrow Cell •Mitochondria •Cytoplasm
- 13. •Reactions of Heme synthesis ALA synthesis Formation of Porphobillinogen Formation of Hydroxymethylbilane Formation of Uroporphyrinogen Synthesis of Coproporphyrinogen Synthesis of Protoporphyrinogen Generation of Protoporphyrin Generation of Heme
- 15. δ ALA DEHYDRATASE 2 δALA STEP 2
- 16. STEP 3
- 17. STEP 4
- 18. STEP 5
- 19. 3 4 5
- 20. STEP 6 STEP 8 STEP 7
- 22. Regulation of heme synthesis
- 23. • Drugs like barbiturates induce heme synthesis. • Large no. of drugs results in a significant increase in hepatic ALAS1 activity. These drugs are metabolized by the microsomal CYP (cytochrome P450) monooxygenase system, a hemeprotein oxidase system found in liver. • In response to these drugs, the synthesis of CYP proteins inc. and dec conc. Of heme. • ALA dehydratase are inhibited by lead. So lead toxicity causes anemia.
- 25. 1. Major sites of heme synthesis liver and bone marrow (erythroblasts). 2. Matured red blood cells have no mitochondria, so can’t synthesize heme. 3. The substrates mainly include succinyl-CoA, glycine, Fe2+ . 3. First and last 3 reactions take place in mitochondria, others in cytoplasm Summary
Editor's Notes
- Biosynthesis of porphobilinogen. ALA synthase occurs in the mitochondria, whereas ALA dehydratase is present in the cytosol. The substrates are succinyl-CoA and glycine The product is delta-aminolevulinic acid (ALA). An essential cofactor is pyridoxal phosphate (vit B-6). This is the rate-limiting reaction of heme synthesis in all tissues, and it is therefore tightly regulated.
- The substrates are two molecules of ALA. The product is porphobilinogen, the first pyrrole. ALA dehydratase is a -SH containing enzyme. • It is very susceptible to inhibition by lead.
- Conversion of porphobilinogen to uroporphyrinogens. Uroporphyrinogen synthase I is also called porphobilinogen (PBG) deaminase or hydroxymethylbilane (HMB) synthase.
- Decarboxylates the acetic acid groups, converting them to methyl groups.
- Catalyzes the conversion of two propionic acid groups to vinyl Groups Protoporphyrinogen IX oxidase converts the methylene bridges between the pyrrole rings to methenyl bridges. Ferrochelatase adds Fe++ to protoporphyrin IX, forming heme. • The enzyme requires Fe++, ascorbic acid and cysteine (reducing agents). • Ferrochelatase is inhibited by lead.
- Barbiturates