jaundice Flashcards
(43 cards)
what are the components of hemoglobin ?
Protein part —> globin ( amino acids )
Non-protein part —> Heme ( porphyrin + iron )
heme act as prosthetic group ( permanent non amino acid group associated with proteins )
what is porphyrin ?
cyclic molecule formed by Linkage of :
4 pyrrole rings through METHENYL BRIDGES (-CH )
with iron atom in the middle
what are 2 states of heme?
oxidized or reduced
Oxidized —-> Ferric
Reduced —> ferrous
examples of molecules containing hemes?
Hemoglobin and myoglobin —> transport O
Cytochrome C –> electron transport
Describe heme structures?
porphyrin + iron
4 Pyrrole rings
each ring has :
Acetyl Group
Propionyl Group
Methenyl Bridges connect the 4 PYRROLE RINGS —> porphobilinogen
All of these are involved in the synthesis of porphyrins and porphyria disorders
describe the degradation of hemoglobin ?
After about 120 days the RBCS will be degraded by RETICULOENDOTHELIAL SYSTEM ( THE LIVER AND SPLEEN )
Globin —> protein part —> will be recycled for making other proteins in the body or for energy production
Heme –> Non protein –> will metabolized into several intermediates which the body will get rid of it
85% of degrade heme comes from the hemoglobin while the rest comes from other heme containing proteins
what is the first step of degradation of heme?
Porphyrin ring is opened by OXIDATION REACTION
Catalysed by the MICROSOMAL HEME OXYGENASE
what does microsomal heme oxygenase require ?
NADPH
O2
what is the result of the oxidation reaction of the porphyrin rings?
Linear biliverdin
Carbon monoxide (CO)
Release of iron —> recycled
describe the 2nd step of degradation of heme?
GREEN BILIVERDIN IS REDUCED TO RED/ORANGE BILIRUBIN
via biliverdin reductase ( Require NADPH )
Bilirubin is relatively insoluble
What does bilirubin bind to transport to the liver?
ALBUMIN
non covalently
it binds to bilirubin cuz its relatively insoluble
( WHEN ITS BOUND TO ALBUMIN ITS NOT DANGEORUS BUT UNBOUND BILIRUBIN WHICH IS DANGEROUS TO THE BRAIN )
some drugs like SULPHONAMIDES DISPLACES BILIRUBIN FROM ALBUMIN —> UNBOUND BILIRUBIN —> NEURAL DAMAGE
Describe conjugation of bilirubin?
In the hepatocytes :
Bilirubin dissociate from ALBUMIN and binds to INTRACEULLULAR PROTEIN LIGANDIN
What enzymes responsible for conjugating bilirubin ?
Microsomal bilirubin UDP glucuronosyltransferase / bilirubin UGT
Conjugate bilirubin to two molecules of GLUCURONIC ACID
Bilirubin + Glucuronic acid = Bilirubin diglucuronide / conjugated bilirubin
what is the importance of conjugation ?
mechanism in the liver to INCREASE SOLUBILITY OF METABOLITES to FACILITATE EXCRETION
done by covalent bonding with another group
in this case bilirubin + glucuronic acid = more water soluble= easy excretion
what is crigler-najjar 1 and 2 and Gilbert syndrome ?
Deficiency in Bilirubin UG transferase enzyme
cant conjugate bilirubin
gilbert syndrome —> benign
Crigler najjar 1 and 2 - more serious
where does glucuronic acid come from?
UDP glucuronic acid is a donor of glucuronic acid
UDP glucose is converted to glucuronic acid by oxidation reaction that is CATALYSED BY UDP GLUCOSE DEHYDRODENASE
Glucuronic acid can obtained via various ways :
From lysosomal degradation of glycosaminoglycans ( GAGS
Diet
From glucose 6 phosphate via The uronic acid pathway
what is the end product of glucuronic metabolism?
Xylulose 5 phosphate that feeds PPP
What are the uses of UDP glucuronic acid ?
Glycosylation of GAGS
other gulcuronidation reactions
how does conjugated bilirubin transported?
ACTIVELY transported against concentration gradient into BILE CANALIUCILI and then into the BILE
Bile canaliculi ——–> Bile
what happens in liver disease ?
the energy dependent active transport is disturbed
Unconjugated bilirubin UCB is normally not secreted in the BILE
what is DUBIN JOHNON SYNDROME?
Deficiency in the transporter of conjugated bilirubin
what happens to conjugated bilirubin when it leaves the liver?
Hydrolysed and reduced by bacteria in the gut
YIELDING UROBILINOGEN —> colorless compound
what happens to Urobilinogen?
In intestines :
Urobilinogen is oxidized by the intestinal BACTERIA ———-> STEROCOBILIN
which gives feces brown color
what happens to some urobilinogen that doesnt get converted to stercobilin ?
Re-absorbed into the gut and enter the portal blood :
Re secreted into the bile
Urobilinogen reach the kidney —> converted to yellow urobilin