CATABOLISM OF HEME

1. CatabolismofHeme
BY
VANA JAGAN MOHAN RAO M.S.Pharm, MED.CHEM
NIPER,KOLKATA
Asst. Professor, MIPER- KURNOOL
Email: jaganvana6@gmail.com

2. Catabolism of heme
Heme
Bile pigments ( Bilirubin and Biliverdin)
Sites
Reticulo-
endothelial cells of
liver, spleen and
bone marrow.
Sources
• Senescent RBC’s (80%)
• Other heme containing proteins
(Myoglobin, cytochromes) (10%)
• Ineffective erythropoiesis (10%)
Heme degraded
per day – 6gm

3. Steps of Heme degradation
Formation of bilirubin
Uptake of bilirubin by liver
Conjugation of bilirubin
Fate of bilirubin
• Secretion of bilirubin into bile
• Formation of urobilins in the intestine
• Excretion in urine and stool

4. Formation of Bilirubin
Heme
Heme
oxygenase
O2, NADPH +
H+
NADP+
Fe3+, CO
Biliverdin
Biliverdin
reductase
NADPH + H+
NADP+
Bilirubin
Alb Alb
Alb
Alb
Bil
Alb
RBC
Bilirubin-Albumin
Complex
Macrophage
FORMATION OF BILIRUBIN

5. UPTAKE & CONJUGATION OF BILIRUBIN IN LIVER
Alb Bil
Bilirubin
Bilirubin
diglucuronide
Liver
Intestine
Bile
Rate limiting step
Mediated by Multispecific Organ Anion
Transporter (MOAT)
Induced by phenobarbitone
Bilirubin-glucuronyl
transferase
2 UDP-
glucuronic
acid
2 UDP

6. Bilirubin
diglucuronide
Bilirubin Urobilinogen Stercobilinogen
Stercobilin  ToFeces
Urobilinogen
Urobilinogen
Urobilin
To Urine
Urobilinogen
Intestine
Liver
Kidney
Entero-hepatic circulation
FATE OF BILIRUBIN

7. Normal plasma level
• Total bilirubin = 0.2-0.8 mg/dl
• Unconjugated bilirubin = 0.2-0.6 mg/dl
• Conjugated bilirubin = 0-0.2 mg/dl
Plasma bilirubin > 1 mg/dl is known
as hyperbilirubinemia
• Levels between 1-2 mg/dl  Latent
jaundice
• Level > 2mg/dl Bilirubin diffuses into
tissues producing yellowish discoloration
of sclera, conjunctiva, skin and mucous
membrane resulting in jaundice
Jaundice
Hemolytic
Hepatocellular
Obstructive
PLASMA BILIRUBIN