metabolsim of heme

Question 1

where is heme biosynthesis located

Answer 1

liver and erythrocyte producing cells of bone marrow

Question 2

where are the steps in heme syntheiss located

Answer 2

1 and 3 last–>mitochondria

rest–>cytosol

Question 3

what is the rate limiting step in prophyrin biosynthesis

Answer 3

ala syntahse, need pyroxidal phpshate

Question 4

act and inhi of alas1

Answer 4

act: iron

– stronger drugs like

inhi: heme

Question 5

act and inhib of ala dehydartase

Answer 5

inhi by heavy metal ions like lead

Question 6

what is hydrocymethylbilane

Answer 6

linear tetrapyrrole

Question 7

difference between those with enzyme defect prior to synthesis and those under syntheis

Answer 7

those with enxymoe defect prior to synthesis manifest: abdominal and neuroppsychiatric signs

enxyem defect leafing to accumulation–>photosensityvity

Question 8

what is chronic hepatic prophyria associated with

Answer 8

• severe deficinet of UROD(urophorphyrinogen)

clinically
-hepatic iron overloas
-exposere to sunlight
-alcohol ingesiton
-estrogen therapy
-presence of hepatitis B or C
-HIV infecitons

Question 9

acute hepatifc porphyria are characterized by

Answer 9

acute attacks of GI
neuropsychiatric
motor symptoms accompanied by photosensitivity

• symtpmes are increased by use of drugs like barbiturates and ethanol

Question 10

how can acute prophyria be treted

Answer 10

intravenous injection of hemin and glucose

Question 11

how is heme degradated

Answer 11

by mononuclear phagocyte system in liver anf spleen

Question 12

at what step is the opening of porphyrin ring

Answer 12

biliverdin formaiton by heme oxygenase

three successive ocygenations happens.

Question 13

why is bilirubin transported throug blood to liver by binding of albumin

Answer 13

beacuse it is only slighlty soluble in plasma

then it enter hepatocyte via facilitated diffusion and binds to intracellular protiens-protein ligandin

Question 14

how is bilirubin solubility increase and what can we conclude with

Answer 14

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

Question 15

what is the rate limiting step oof heme degradationq

Answer 15

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.

Question 16

pre hepatic /hemolytic

Answer 16

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

Question 17

hepatocellular (hepatic)

Answer 17

• 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

Question 18

obstructive (post hepatic)

Answer 18

• 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,

Question 19

ICTERUS NEONATORUM ( Icterus of newborns)

Answer 19

• 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