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Introduction

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High-Yield Terms

  • Porphyrin: a group of aromatic organic compounds composed of 4 modified pyrrole subunits interconnected at their α-carbon atoms via methine bridges

  • Porphyria: any of a group of rare inherited or acquired disorders of enzymes involved in the production of the porphyrins and heme

  • Hemin: protoporphyrin IX containing a ferric (Fe3+) iron, as opposed to heme which contains ferrous (Fe2+) iron

  • Reticuloendothelial cells: a collective term for cells of the immune system that primarily comprises macrophages and monocytes but may include all phagocytic cells

  • Bilirubin: open chain yellowish breakdown product of heme catabolism

  • Kernicterus: bilirubin-induced brain dysfunction, also called bilirubin encephalopathy

  • Sideroblastic anemia: a disease in which the bone marrow produces ringed sideroblasts rather than healthy erythrocytes, sideroblasts are abnormal nucleated erythroblasts with granules of iron in perinuclear mitochondria

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Porphyrins and Heme

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The porphyrins (Figure 33-1) are a group of aromatic organic compounds composed of 4 modified pyrrole subunits interconnected at their α-carbon atoms via methine bridges (=CH–). These compounds are highly conjugated systems and as such they typically have very intense absorption bands in the visible region and may be deeply colored. Indeed, the name porphyrin comes from a Greek word for purple. In humans, the most clinically significant porphyrins are the hemes; heme a, heme b, and heme c. Heme b is called protoporphyrin IX and it contains 4 methyl, 2 vinyl, and 2 propionic acid substituents. Heme b is the prosthetic group that binds oxygen in erythrocytes and is the pigment that induces the reddish color of blood. Heme a and heme c are prosthetic groups of several cytochromes, particularly of the electron transport chain (Chapter 17). Many additional proteins contain a heme prosthetic group with the largest family of such proteins being the cytochrome P450 (CYP) enzymes, many of which are involved in xenobiotic metabolism in the liver.

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FIGURE 33-1:

The porphyrin molecule. Rings are labeled I, II, III, and IV. Substituent positions on the rings are labeled 1, 2, 3, 4, 5, 6, 7, and 8. The methyne bridges (=HC—) are labeled α, β, γ, and δ. The numbering system used is that of Hans Fischer. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper's Illustrated Biochemistry, 29th ed. New York: McGraw-Hill; 2012.

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Synthesis of Porphyrins and Heme

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The first reaction in heme biosynthesis takes place in the mitochondrion and involves the condensation of 1 glycine and 1 succinyl-CoA by the pyridoxal phosphate-containing enzyme, δ-aminolevulinic acid synthase (ALAS) (Figure 33-2). Delta-aminolevulinic acid (ALA) is also called 5-aminolevulinic acid. This reaction is both the rate-limiting reaction of heme biosynthesis and the most highly regulated reaction. There are 2 forms of ALAS. ALAS1 is considered a house-keeping gene and is expressed in ...

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