CBB 37: Heme Metabolism

Heme Synthesis Regulation

Regulated primarily through the isoforms of ALA synthase, specifically ALAS1 in the liver and ALAS2 in erythroid cells.

Rate-limiting enzyme in heme synthesis

δ-aminolevulinic acid synthase (ALA synthase), crucial for the production of heme.

ALAS1

Isoform located in liver/non-erythroid tissues, inhibited by heme but induced by increased demand for heme.

ALAS2

Isoform located in erythroid cells, not inhibited by heme; regulated by iron availability.

Mechanism of lead poisoning

Inhibits ALA dehydratase and ferrochelatase leading to decreased heme synthesis and accumulation of ALA and protoporphyrin.

Primary anemia caused by vitamin B6 deficiency

Sideroblastic anemia due to decreased production of δ-ALA.

Acute Intermittent Porphyria (AIP)

A type of porphyria caused by deficiency of porphobilinogen deaminase resulting in abdominal pain and neuropsychiatric symptoms.

Porphyria Cutanea Tarda (PCT)

A type of porphyria characterized by uroporphyrinogen decarboxylase deficiency, causing photosensitivity and blistering skin lesions.

Bilirubin UDP-glucuronosyltransferase

An enzyme responsible for the conjugation of bilirubin, its deficiency leads to conditions like Crigler-Najjar and Gilbert syndromes.

Difference between unconjugated and conjugated bilirubin

Unconjugated bilirubin is insoluble and bound to albumin, while conjugated bilirubin is water-soluble and can be excreted.

Types of jaundice

Includes hemolytic, hepatocellular, obstructive, and newborn jaundice, each with distinct causes and characteristics.

Key symptom of hemolytic jaundice

Elevated unconjugated bilirubin due to excess RBC breakdown.

Key feature of obstructive jaundice

Elevated conjugated bilirubin due to blocked bile flow, resulting in pale stools and dark urine.

Clinical significance of bilirubin levels

Measurement of bilirubin helps diagnose the cause of jaundice.