Internal dynamics of heme-based sensor proteins studied using ...
HEME SYNTHESIS DR AMINA TARIQ BIOCHEMISTRY. HEME PROTEINS These are a group of specialized proteins...
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Transcript of HEME SYNTHESIS DR AMINA TARIQ BIOCHEMISTRY. HEME PROTEINS These are a group of specialized proteins...
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HEME SYNTHESISDR AMINA TARIQBIOCHEMISTRY
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HEME PROTEINSThese are a group of specialized
proteins that contain heme and globin.
Heme is the prosthetic part and globin is the protein part.
97% is the globin part and the rest 3% is the heme part.
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GLOBULAR HEME PROTEINS
Role of heme group is dictated by the environment.
Examples: a. Cytochromes b. Catalase c. Hemoglobin d. Myoglobin
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PORPHYRIN METABOLISMPorphyrins are cyclic compounds.They bind metal ions, mostly Fe2+
or Fe 3+
The most prevalent metalloporphyrin in humans is Heme.
Heme is the prosthetic group for myoglobin, hemoglobin , cytochromes, catalase and tryptophan pyrrolase.
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Heme consists of one ferrous ion in the center of a tetrapyrrole ring of protoporphyrin IX.
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Structure of PorphyrinsThese are cyclic molecules.Formed by the linkage of four
tetrapyrrole rings, through methenyl bridges.
Structural Features:1. Side chains- All the porphyrins
vary in the nature of their side chains that are attached to their pyrrole rings.e.g.
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Uroporphyrin- acetate and propionate
Coproporphyrin- methyl and propionate
Protoporphyrin IX- vinyl, methyl and propionate
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2. The side chains can be ordered in four different ways, designated as I- IV.
Only Type III porphyrins are physiologically important. They have an asymmetric distribution. e.g.
AP, AP, AP, AP- Type I
AP, AP, PA, AP- Type III
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3. Porphyrinogens : These are the precursors of porphyrins. They are colorless.
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STEPS OF SYNTHESIS OF HEME
Major Sites:1. Liver (heme proteins-
cytochromes)(fluctuating)2. Bone marrow (RBC)(constant).3. Initial and the last three steps
occur in the mitochondria4. Intermediate steps in the cytosol.5. RBC’s have no mitochondria,
unable to synthesize heme.
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Glycine + succinyl CoA
δ-aminolevulinic acid(ALA) Enzyme: Mitochondrial enzyme δ-aminolevulinate synthase − Hemin, Heme
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Reaction requires pyridoxal phosphate as a co- enzyme.
It is the rate limiting stepInhibited by end product hemin
(heme).Drugs such as phenobarbitol,
griseofulvin or hydantoin- increase the activity of ALA synthase.
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These drugs are metabolized by microsomal cytochromes
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δ-aminolevulinic acid(ALA) (2 mol condense)
Porphobilinogen Enzyme: δ-aminolevulinic acid
dehydratase − Lead
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Porphobilinogen( 4 molecules condense)
Hydroxymethylbilane
Enzyme: Hydroxymethylbilane synthase
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Hydroxymethylbilane (ring closure and isomerization)
Uroporphyrinogen IIIEnzyme- Uroporphyrinogen III
synthase
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Uroporphyrinogen III
Coporphyrinogens III Enzyme: Uroporphyrinogen
decarboxylase
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Coporphyrinogens III
Protoporphyrinogen IXEnzyme: Coporphyrinogens Oxidase
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Protoporphyrinogen IX
Protoporphyrin IX Enzyme: Protoporphyrinogen
oxidase
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Protoporphyrin IX
HemeEnzyme: Ferrochelatase
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Learning ResourcesLippincott's BiochemistryLecture notes