Chapter 31: Porphyrins & Bile Pigments

The biosynthetic pathway of heme is a highly regulated eight-step process that alternates between the mitochondria and the cytosol, initiating with the condensation of succinyl-CoA and glycine. This first step is managed by the rate-limiting enzyme delta-aminolevulinate synthase, which exists in two forms: one for general tissue needs and another specific to red blood cell precursors. The text details how heme serves as a feedback inhibitor to regulate its own production, ensuring cellular balance. Porphyrins themselves are cyclic molecules with unique physical properties, including a distinct absorption band and the ability to fluoresce red under ultraviolet light due to their conjugated double bond systems. When genetic or acquired defects impair the enzymes in this pathway, it leads to a group of diseases known as porphyrias, which often present with symptoms like skin photosensitivity, abdominal distress, and neurological issues. Beyond synthesis, the chapter provides an in-depth look at heme catabolism, where the breakdown of old red blood cells produces biliverdin and then bilirubin. Because bilirubin is not easily dissolved in water, it must be transported by albumin to the liver, where it undergoes conjugation with glucuronic acid to facilitate its excretion into bile. Clinical abnormalities in these processes result in hyperbilirubinemia, commonly recognized as jaundice. The material distinguishes between different types of jaundice—pre-hepatic, hepatic, and post-hepatic—and describes genetic conditions such as Gilbert syndrome and Crigler-Najjar syndrome, providing a framework for using laboratory tests like direct and indirect bilirubin levels to diagnose specific metabolic failures.