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After studying this chapter, you should be able to:

  • Identify the two amphibolic intermediates from which heme is synthesized.

  • Name the key regulated enzyme of hepatic heme biosynthesis.

  • Explain why, although porphyrinogens and porphyrins both are tetrapyrroles, porphyrins are colored whereas porphyrinogens are colorless.

  • Appreciate that the some of the enzymes of heme biosynthesis are mitochondrial and others are cytosolic.

  • Indicate which steps in the conversion of heme to bilirubin are cytosolic and which are mitochondrial.

  • Understand the causes and general clinical pictures of the various porphyrias.

  • Explain the biochemical nature of jaundice, name some of its causes, and suggest how to approach determining its biochemical underpinnings.

  • Explain what is meant by “direct bilirubin” and “indirect bilirubin.”


The biochemistry of the porphyrins and of the bile pigments are closely related topics. Heme is synthesized from porphyrins and iron, and the products of degradation of heme are the bile pigments and iron. The biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins, and the porphyrias, a group of diseases caused by abnormalities in the pathway of porphyrin biosynthesis. A much more common clinical condition is jaundice, a consequence of an elevated level of plasma bilirubin, due either to overproduction of bilirubin or to failure of its excretion. Jaundice occurs in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas.


Porphyrins are cyclic compounds formed by the linkage of four pyrrole rings through methyne (ÓHC—) bridges (Figure 31–1). In the naturally occurring porphyrins, various side chains replace the eight numbered hydrogen atoms of the pyrroles. Figure 31–2 shows a shorthand representation of these substitutions. Figures 31–3 and 31–4 illustrate these substituents on selected porphyrins.


The porphyrin molecule. Rings are labeled I, II, III, and IV. Substituent positions are labeled 1 through 8. The four methyne bridges (ÓHC—) are labeled α, β, γ, and δ.


Shorthand representation of a porphyrin, uroporphyrin III. Left: Numerals 1 through 8 correspond to those of Figure 31–1. Right: The substituents on uroporphyrin III are A = acetate (—CH2COO) and P = propionate (—CH2CH2COO). Notice the asymmetry of the substituents on ring 4.


Uroporphyrins and coproporphyrins. A = acetate; M = methyl; P = propionate. Notice that the positions of the highlighted acetate and propionate substituents are reversed in uroporphyrins I and II, and in coproporphyrins I and II.


Addition of iron to protoporphyrin III forms heme...

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