Bilirubin

TISNA SENDY PRATAMA

BIOKIMIA FK UNSOED
Catabolism of Heme
Produces Bilirubin
Erythrocytes normally have a lifespan of approximately 120
days.
Senescent or damaged erythrocytes are phagocytosed by
macrophages of the reticuloendothelial system (RES)
present in the spleen and liver.
200 billion erythrocytes (40 mL of blood) are catabolized /
day 70-kg human turns over approximately 6 g of
hemoglobin daily
globin is degraded to its constituent amino acids, the
released iron enters the iron pool, and all products are
reused.
The iron-free porphyrin portion of heme is also degraded,
mainly in the reticuloendothelial cells of the liver, spleen,
and bone marrow.
 The catabolism of heme from all heme proteins
is carried out in the microsomal fraction of
cells by heme oxygenase
The iron of the heme that reaches heme
oxygenase has usually been oxidized to its
ferric form (hemin)

Fe3+-Heme + 3 O 2 + 7 e-
biliverdin + CO + Fe3+
seven electrons provided by NADH and NADPH-
cytochrome p450 reductase.
1 g of hemoglobin yields about 35 mg of
bilirubin,
human adults form 250 to 350 mg of
bilirubin per day.
Bilirubin Is Transported to
the Liver Bound to Serum
Albumin

bilirubin bound to serum albumin is readily

transported to the liver.
The high-affinity site of albumin can bind
approximately 25 mg of bilirubin/100 mL of
plasma
Uptake of Bilirubin by
Liver
parenchymal Cells
Bilirubin is removed from albumin
and taken up
at the sinusoidal surface of hepatocytes by a
large capacity.
Once internalized, bilirubin binds to cytosolic
proteins such as glutathione S-transferase,
previously known as a ligandin, to prevent
bilirubin from reentering the blood stream.
Conjugation of
Bilirubin With
Glucuronate
Bilirubin is nonpolar, and would persist in cells (eg, bound
to lipids) if not converted to a more water-soluble form.
Bilirubin is converted to a more polar molecule by
conjugation with glucuronic acid.
A bilirubin-specific UDP-glucosyl transferase of the
endoplasmic reticulum catalyzes stepwise transfer to
bilirubin of two glucosyl moieties from UDP-glucuronate:
Bilirubin + UDP-glucuronate bilirubin
monoglucuronide + UDP
Bilirubin monoglucuronide + UDP-glucuronate
bilirubin diglucuronide + UDP
Secretion of Bilirubin
Into the Bile
Secretion of conjugated bilirubin into the bile
occurs by an active transport mechanism,
which probably is rate-limiting for the entire
process of hepatic bilirubin metabolism.
The protein involved is a multispecific
organic anion transporter (MOAT) located in
the plasma membrane of the bile canaliculi
Intestinal Bacteria
Reduce Conjugated
Bilirubin to
Urobilinogen
When conjugated bilirubin reaches the terminal

ileum and the large intestine, the glucuronosyl
moieties are removed by specific bacterial -
glucuronidases.
Subsequent reduction by the fecal flora forms a
group of colorless tetrapyrroles called
urobilinogens.
mall portions of urobilinogens are reabsorbed in
the terminal ileum and large intestine
and subsequently are reexcreted via the
enterohepatic urobilinogen cycle.
 Under abnormal conditions, particularly when
excessive bile pigment is formed or when liver
disease disrupts this intrahepatic cycle,
urobilinogen may also be excreted in the urine
Most of the colorless urobilinogens formed in
the
colon are oxidized there to colored urobilins
and excreted in the feces. Fecal darkening upon
standing in air results from the oxidation of
residual urobilinogens to urobilins.
Apakah perbedaan bilirubin
total, direct dan indirect?
Referensi

Harper's Illustrated Biochemistry, 30E