metabolsim of heme Flashcards
where is heme biosynthesis located
liver and erythrocyte producing cells of bone marrow
where are the steps in heme syntheiss located
1 and 3 last–>mitochondria
rest–>cytosol
what is the rate limiting step in prophyrin biosynthesis
ala syntahse, need pyroxidal phpshate
act and inhi of alas1
act: iron
– stronger drugs like
inhi: heme
act and inhib of ala dehydartase
inhi by heavy metal ions like lead
what is hydrocymethylbilane
linear tetrapyrrole
difference between those with enzyme defect prior to synthesis and those under syntheis
those with enxymoe defect prior to synthesis manifest: abdominal and neuroppsychiatric signs
enxyem defect leafing to accumulation–>photosensityvity
what is chronic hepatic prophyria associated with
- severe deficinet of UROD(urophorphyrinogen)
clinically
-hepatic iron overloas
-exposere to sunlight
-alcohol ingesiton
-estrogen therapy
-presence of hepatitis B or C
-HIV infecitons
acute hepatifc porphyria are characterized by
acute attacks of GI
neuropsychiatric
motor symptoms accompanied by photosensitivity
- symtpmes are increased by use of drugs like barbiturates and ethanol
how can acute prophyria be treted
intravenous injection of hemin and glucose
how is heme degradated
by mononuclear phagocyte system in liver anf spleen
at what step is the opening of porphyrin ring
biliverdin formaiton by heme oxygenase
three successive ocygenations happens.
why is bilirubin transported throug blood to liver by binding of albumin
beacuse it is only slighlty soluble in plasma
then it enter hepatocyte via facilitated diffusion and binds to intracellular protiens-protein ligandin
how is bilirubin solubility increase and what can we conclude with
hepatocyte: addition of teo molecules of glucuronic acid by conjugation (UDP-glucuronosyltransferase)
- UDP -glucuronic acid is glucuronate donor
BILIRUBIN DIGLUCURONIDE/CONJUGATED IS MORE SOLUBLE THAN BILIRUBIN
what is the rate limiting step oof heme degradationq
CB is actively transported against
a concentration gradient into the bile canaliculi and then into
the bile. This energy-dependent, rate-limiting step is
susceptible to impairment in liver disease.
pre hepatic /hemolytic
normal bilirubin production: 250 – 350 mg/ 24 h
- functional capacity 3 000 mg/ 24 h
- causes: excesive hemolysis (malaria, sickle cell anemia … )
- biochemical findings:
a/ ^ production of CONJUGATED BILIRUBIN => blood bilirubin
b/ ^ UROBILINOGEN in urine
c/ ^ UROBILINOGEN in blood
d/ faeces - polycholic
UCB ARE ABNORMALLY ELEVATED
hepatocellular (hepatic)
- damage tp liver cells –>unconjugated hyperbilrubina becasue of decreased conjugation
- causes: hepatitis, cirhosis, toxic damage ….
- biochemical findings:
a/ low BILIRUBIN uptake
b/ low production of CONJUGATED BILIRUBIN
c/ ^ UNCONJUGATED BILIRUBIN in blood and urine
d/ ^ UROBILINOGEN in plasma
e/ ^ UROBILINOGEN in urine
f/ dark color of urine
g/ faeces have normal color, on top of disorder may be lighter
h/ ^ ALT, AST - other clinical symptoms: nauzea, anorexia
UCB AND CB ARE ABNORMALLY ELEVATED
obstructive (post hepatic)
- obstruction of common bile duct
- causes: stones, tumor of ductus choledochus, pancreatic cancer in the
head of pancres - biochemical findings:
a/ ^ production of CONJUGATED BILIRUBIN
b/ low UROBILINOGEN in urine (on the top of disorder Ø)
c/ low UROBILINOGEN in blood (on the top of disorder Ø)
d/ faeces: lighter, acholic - other clinical syptoms: intestinal pain, nauzea
URINARY UROBILINOGEN IS ABSEBT
STOOL ARE OAKE CLAY COLOR,
ICTERUS NEONATORUM ( Icterus of newborns)
- natural conversion of fetal hemoglobin (α2γ2) to adult hemoglobin (α2β2)
- icterus lasts 3-4 days, physiological reaction
- bilirubin is lipophilic → deposition in the brain („kernicterus“) → mental
retardatio
