This video is about heme catabolism or heme degradation. Heme is degraded into bilirubin in a heme degradation pathway. Heme degradation pathway or heme degradation biochemistry is important for understanding different types of bilirubin being elevated in jaundice. Types of jaundice can be classified based on the type of bilirubin being elevated in the blood. Heme catabolism or heme degradation is important concept Heme Catabolism (Heme Degradation Pathway) heme catabolism Bilirubin metabolism ( Heme catabolism) Heme Catabolism and Degradation Pathway - Biochemistry Lesson Bilirubin metabolism Heme catabolism Heme catabolism || Bilirubin metabolism || #Biochemistry steps Introduction Bilirubin formation pathway Transport of bilirubin to liver Uptake of bilirubin in liver Conjugation of bilirubin Excretion of bilirubin in bile canaliculi Fate of conjugated bilirubin in intestine Entero-hepatic circulation of urobilinogen Final excretion of UBG and SBG As the channel name suggests, our channel will be a perfect lounge for the malayali medicos..we wil be covering videos which will be like lecture classes related to the subjects biochemistry and microbiology in which we are specialised.. It will be a better learning experience for the students especially for those who are not able to understand and follow the normal classes in college..we assure the students that you will get a basic idea regarding the topic and extra reading can be done from the reference textbooks... If you like my video #like #comment #subscribe my channel don't forget to subscribe my channel Qualification Ahlad.T.O MSc MLT (Biochemistry) Assistant Professor Baby memorial college of allied Health science Kozhikode Our Partner Channel Health & Voyage channel link - https://youtu.be/nzKqRVjlwc0 Heme catabolism Heme degradation in macrophages Bilirubin transport with albumin Bilirubin metabolism 1. Uptake by hepatocytes by facilitated diffusion 2. Conjugation of unconjugated bilirubin 3. Secretion in to bile canaliculi by active transport through MRP 2 Congenital causes UNCONJUGATED BILIRUBIN INCREASE 1. Crigler Najjar type 1 2. Crigler Najjar type 2 3. Gilbert syndrome Conjugated bilirubin increase 1. Dubin Johnson syndrome 2. Rotor syndrome #Mallu #Microbiology #Biochemistry #MalluMedicosLounge #HealthAndVoyage #How to take online class

1. HEME CATABOLISM
&
BILIRUBIN METABOLISM
By
Ahlad.T.O
Assistant Professor
Baby Memorial College
Kozhikode
MALAYALAMVIDEO CLASS UPLOADED INYOUTUBE CHANNEL- MALLU MEDICOS LOUNGE

2. STRUCTURE OF HEME
• Four pyrrole rings are
linked by α - methenyl
bridges to form a cyclic
tetrapyrrole (porphyrin
nucleus).

3. HEMOPROTEINS (HEME
CONTAINING PROTEINS)
• Hemoproteins are proteins that have heme as their prosthetic group.
– Hemoglobin
– Cytochrome P450 mono-oxygenases – present abundantly in the liver
– Myoglobin
– Cytochrome c oxidase (complex IV of ETC)
– Catalase
– Tryptophan pyrrolase

4. HEME DEGRADATION
• Degradation of heme takes place in the
reticuloendothelial system (RES).
• RES is a system of mononuclear phagocytes
(monocytes and macrophages) found in spleen,
liver, bone marrow etc.

5. • After ~120 days in circulation, red
blood cells are taken up by
macrophages of the
reticuloendothelial system (RES).
• 85% of heme for degradation comes
from senescent RBCs.
• 15% is derived from
cytochromes, myoglobin,
immature RBCs, etc. Electron micrograph of a macrophage
phagocytosing an erythrocyte.
Araki et al. (2003). J Cell Sci, 116 pg
247

6. • Hemoglobin undergoes degradation
– globin – degraded to constituent amino acids (is
reused).
– iron removed from heme, enters iron pool in the
body (is reused OR stored as ferritin in the cell).
– iron-free porphyrin ring degraded toform
bilirubin.

7. NADPH

8. YELLOW
FEW HOURS
AFTER INJURY
FEW DAYS
AFTER INJURY
RED

9. BILIRUBIN IN CIRCULATION
• Bilirubin only slightly soluble in water.
• This form is called unconjugated bilirubin.
• Transported in plasma by binding to albumin.
• Binding with albumin prevents bilirubin from
diffusing into tissue.
• Unconjugated bilirubin does NOT appear in
urine.

10. CLINICAL RELEVANCE OF UNCONJUGATED
BILIRUBIN BINDING TO ALBUMIN
• Increased amounts of unconjugated bilirubin in blood, that
exceeds the capacity of albumin to bindit (> 25 mg/dL),
results in it diffusing intotissue.
• Can lead to kernicterus in the newborn – deposition of
bilirubin, especially in the basal ganglia of brain.

11. 1. UPTAKE OF BILIRUBIN IN THE LIVER
• In the liver, bilirubin dissociates from albumin.
• It is taken up at the sinusoidal surface of
hepatocytes by facilitated diffusion (carrier-
mediated).
• Once bilirubin enters the hepatocytes, it binds to
cytosolic proteins – ligandin (protein Y) and Z protein.

12. 2. CONJUGATION WITH GLUCURONIC ACID
• Bilirubin is non-polar.
• Hepatocytes convert bilirubin into a polar form
by adding glucuronic acid to it.
• Process called conjugation.
• Conjugated bilirubin is water-soluble and
excreted in the bile.

13. BILIRUBIN
BILIRUBIN DIGLUCURONIDE
UDP – glucuronic acid
UDP
UDP
Bilirubin UDP–
Glucuronyl
transferase
Bilirubin UDP–
Glucuronyl
transferase
BILIRUBIN MONOGLUCURONIDE (15% in bile)
UDP – glucuronic acid
(85% in bile)

14. CONJUGATION WITH GLUCURONIC ACID
• UDP- glucuronic acid is the donor.
• Catalyzed by bilirubin UDP-glucuronosyl
transferase.
• Under physiological conditions, almost all
bilirubin secreted into bile is conjugated.

15. 3. SECRETION OF CONJUGATED BILIRUBIN
INTO BILE
• Conjugated bilirubin is excreted into the
biliary canaliculi.
• Occurs by active transport process.
• This step is probably rate limiting for the entire
process of hepatic bilirubin metabolism.

16. 4. METABOLISM OF CONJUGATED
BILIRUBIN IN THE INTESTINE
• When conjugated bilirubin reaches the distal part of the
small intestine, the glucuronides are removed by
specific bacterial enzymes (β - glucuronidase)
• Bilirubin reduced by bacterial enzymes to a group
of colourless compounds called urobilinogens.

17. FATE OF UROBILINOGEN
• Most of urobilinogen remains in the gut.
• Is oxidized by intestinal bacteria to form
stercobilinogen.
• Stercobilinogen gets oxidized further to
stercobilin, which gives faeces its characteristic
brown colour.

18. • A small amount (10%) of urobilinogen is absorbed
from the gut and enters the portal circulation.
• A small fraction of urobilinogen in circulation is taken
up by the liver, excreted in bile and re- enters the gut.
This constitutes enterohepatic urobilinogen cycle.
üSmall portion of urobilinogen in circulation may be
excreted in urine