METABOLISM

IN THE LIVER
DESAK MADE WIHANDANI

Learning Task:
Describe the liver processes bilirubin
Descrice the biochemical causes of
hyperbilirubinemia (jaundice) and its
classification

Carbohydrate, Lipid and

Protein metabolism
To storage glucose as glycogen
To form glucose from non-CH sources in
gluconeogenesis
Glycogenolysis
Synthesis and catabolism of cholesterol
Synthesis plasma protein
The Urea cycle and ammonia

HEME SYNTHESIS

PORFIRIN
synthesis

HEME
degradation
BILIRUBIN

HEME SYNTHESIS

8 ENZYMES
- 1, 6, 7 AND 8 : MITOCHONDRIA
- 2, 3, 4 AND 5 : CYTOPLASMA
ALAS 1: KEY REGULATORY ENZYME
DEFECT OF EACH ENZYME PORPHYRIA

PORPHYRIAS
DEFECT THE ENZYME THAT INVOLVED IN
PORPHIRIN METABOLISM
SYMPTOM:

ANEMIA
SKIN SENSITIVE
PHOTOSENSITIVE (-carotene, sunscreen)

PORPHYRIAS
DIAGNOSE:
- CLINICAL AND FAMILY HISTORY
- PHYSICAL EXAMINATION
- LABORATORY
THERAPY:
- SYMPTOMATIC
- GENE THERAPY

BILIRUBIN METABOLISM

3 PROCESS:
- UPTAKE BILIRUBIN
- CONJUGATION
- SECRETION

UPTAKE OF BILIRUBIN
- by hepatocytes
- non soluble Albumin non covalent
- 25 mg tightly bound to albumin
- antibiotics, drugs compete displace

CONJUGATION
-

in the liver
conj. of bilirubin with glucoronic acid
by specific glucoronosyltransferase
convert bili to a polar form excreted in the bile

SECRETION
-

Into bile
Active transport
Diglucoronide bilirubin

Intestine :
diglucoronide bilirubin
-glucoronidase
Urobilinogen (colorless)
oxidized
Urobilin (coloured)
Feces

Metabolism of Heme and

Bilirubin
Insert fig. 18.23
globin
PROTOPORPHYRINE

Sistema RetikuloEndotelial

HYPERBILIRUBINEMIA
Def: Yellow discoloration of skin and
mucosae due to hyperbilirubinemia
(> 1.0mg/dL)
Over production
Failure to excrete
3 mg/dL tissue (yellow)JAUNDICE/ICTERUS
Jaundice occurs in three forms:
- prehepatic
- intrahepatic
- post hepatic

JAUNDICE

JAUNDICE/ICTERUS

JAUNDICE/ICTERUS

HYPERBILIRUBINEMIA

Retention hyperbilirubinemia
over production
unconjugated bilirubin
hemolytic anemia
neonatal physiologic jaundice
(immature hepatic system, >20-25mg/dLKern icterus)

Regurgitation hyperbilirubinemia
obstruction
conjugated bilirubin
choluric jaundice

Bilirubin
- Direct Bilirubin

- Indirect Bilirubin

- Conjugated

- Unconjugated

- Soluble in H2O

- Insoluble in H2O

- 0-20% in plasma

- 80-100% in plasma

- HEPATAL

- PREHEPATAL

THANK YOU