Prophyrin Metabolism And Jaundice(19 Oct)

Porphyrin Metabolism and Jaundice

Dr. Mohammad Akram

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What is Porphyrin?  Porphyrins

are a group of organic compounds of which many occur in nature, most well-known as the pigment in red blood cells. They are heterocyclic macrocycles characterised by the presence of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH-). 2

Structure of Pyrrole

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Introduction Within the body iron exist in two oxidation states: ferrous (Fe2+) or ferric (Fe3+). Because iron has an affinity electronegative atoms such as oxygen, nitrogen and sulfur, these atoms are found at the heart of the iron-binding centers of macromolecules. 4

Cont. Neutral or alkaline pH Fe3+ Acidic pH Fe2+ When in the Fe3+ state, iron will form large complexes with anions, water and peroxides. These large complexes have poor solubility and upon their aggregation lead to pathological changes and interferences in normal function of body. Anion

is negatively charged ion (SO42−) 5

Iron binding proteins For this reason the body must protect itself against the harmful effects of iron. This is the role served by numerous iron-binding proteins.

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Haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Chemical formula of haem is C49 H56 O6N4Fe Prosthetic compound

is a non-protein chemical compound that is bound (either tightly or loosely) to a protein and is required for the protein's biological activity.

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Porphryrin

In other words, organic ring around the Fe2+ Is called a porphyrin.

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Porphyrin Metabolism It is synthesized by glycine and succinate by a series of enzyme-dependent reactions partly located in metochondria and partly in cell cytoplasm Glycine (amino acid) NH2CH2COOH Succinate

is a component of citric acid cycle. (dicarboxylic acid)

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Porphyrin

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porphyrin

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metabolism Although all cells synthesize Haem but the requirements are high in bone marrow and in liver, as Haem containing enzymes are required for the hormone and drug metabolism.

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Biosynthesis of Haem

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Biosynthesis of Haem

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Disorders of Porphyrin The porphyrias are group of disorders resulting from partial deficiencies of enzymes required for the biosynthesis of haem, leading to XS of haem precursors and;  Photosensitivity  neurotoxicity



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Jaundice Jaundice, also known as icterus, is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae (whites of the eyes), and other mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in the blood).

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Jaundice When red blood cells have completed their life span of approximately 120 days, or when they are damaged, their membranes become fragile and prone to rupture. As each red blood cell traverses through the reticuloendothelial system, its cell membrane ruptures when its membrane is fragile enough to allow this. Cellular contents, including hemoglobin, are subsequently released into the blood.

(The reticuloendothelial system (RES), part of the immune system)

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Jaundice The hemoglobin is phagocytosed by macrophages, and split into its heme and globin portions. The globin portion, a protein, is degraded into amino acids and plays no role in jaundice.

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Jaundice Two reactions then take place with the heme molecule. The first oxidation reaction is catalyzed by the microsomal enzyme heme oxygenase and results in biliverdin (green color pigment), iron and carbon monoxide. The next step is the reduction of biliverdin to a yellow color tetrapyrol pigment called bilirubin by cytosolic enzyme biliverdin reductase. This bilirubin is "unconjugated," "free" or "indirect" bilirubin.

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Jaundice Approximately 4 mg per kg of bilirubin is produced each day. The majority of this bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. However approximately 20 percent comes from other heme sources, including ineffective erythropoiesis, and the breakdown of other heme-containing proteins, such as muscle myoglobin and cytochromes.

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Thank you

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