Catabolism of Heme

Intro
The largest repository of Heme in
the human body is in red blood cells.
There is turnover of about 6 g/day
of hemoglobin,
Porphyrin ring is hydrophobic
Iron must be conserved for new
Heme synthesis.
 Senescent RBCs are engulfed by RE
cells
Globin is recycled
Heme is oxidized by Heme oxygenase
to form biliverdin
Biliverdin is acted upon by biliverdin
reductase to form bilirubin
 Bilirubin formed in peripheral tissues
is transported to Liver
Further metabolism proceeds in
three steps
1. Uptake of bilirubin by liver
2. Conjugation of bilirubin
3. Secretion of conjugated bilirubin
1. Liver takes up Bilirubin
Bilirubin is sparingly soluble in water
Bounded by Albumin non covalently
Albumin contains two sites
High affinity site (25mg/100ml Plasma)
Low affinity site
Drugs and antibiotics can compete for high
affinity site
 Contd..
Albumin is removed from bilirubin at
sinusoidal surface of hepatocytes
Carrier mediated saturable system
Once it enters hepatocytes, its
bound temporarily to cytosolic
proteins
Ligandin and Y proteins
 2.Conjugation
Takes place in hepatocytes
UDP Glucuronic acid is involved
Catalyzed by Glucuronosyl
transferase
Forms Bilirubin Diglucuronide and
excreted
 3.Secretion into bile
Occurs by an active transport
mechanism
Rate limiting for entire hepatic
bilirubin metabolism
MRP-2 (Multidrug Resistance like
protein) or MOAT (Multispecific
organic anion Transporter)
 Contd..
Located in Bile canalicular membrane
Hepatic transport is induced by
number of drugs
E.g.. Phenobarbital
Disturbance in the catabolism of
Heme causes variety of clinical
conditions
 When conjugated bilirubin reaches
terminal ileum or large intestine
glucuronide is removed

Intestinal Bacterias can reduce

bilirubin to urobilinogen (colourless)
 In terminal ileum, a small portion of
urobilinogen is reabsorbed and
reexcreted to constitute the
Enterohepatic urobilinogen cycle