Lec 11 heme synthesis

Question 1

structure of Hemeoglobin

Answer 1

Porphyrin ring with iron present at the center (ferrous)

4 5 membered rings (pyrrole)

Question 2

Phase 1 of heme synthesis

Answer 2

Question 3

Phase II of heme synthesis

Answer 3

Question 4

Phase III of heme synthesis

Answer 4

Question 5

Lead poisoning and heme production

Answer 5

Lead inactivates ALA dehydratase and ferrochelatase

ALA and protoporphyrin ix accumulate

ALA is neurotoxic

causes anemia

impact energy production no cytochromes synthesized

Question 6

What is Porphyrias

Answer 6

Question 7

example of porphyrias that affect the erythropoietic

Answer 7

Congenital erythropoietic porphyria

defect in uroporphyrinogen III synthase (erythrocytes)

Photo sensitivity red urine

Auto recessive

buld up uroporphyrinogen I oxidise to uroporphrin I

Question 8

Porphyrias that affect hepatic

Answer 8

Acute intermittent porphyria

defect in PBG deaminase (in liver)

too much ALA and PBG

Auto dom

ab pain and neuro dysfunction

Variegate porphyria (famous people had it)

defect protoporphyrinogen ix oxidase

Auto dom

photosens.

Question 9

porphyria that affect hepatoerythropoietic

Answer 9

Porphyria cutanea tarda (PCT)

most common in us

defect uroporphyrinogen decarboxylase

auto dom

Question 10

Heme degradation is under what system?

Answer 10

Reticulo-endothelial system

Question 11

Globin broken down into what?

what happens to heme?

Answer 11

Globin broken down into aa

heme removed for degradation

Question 12

Difference between heme and bilirubin?

Answer 12

Question 13

What does heme oxygenase require?

what does it release?

Answer 13

oxygen

releases Carbon monoxide

Question 14

What happens to the Fe2+ in heme once broken open?

Answer 14

changes into ferric iron Fe3+

Question 15

Pathway from heme into billirubin

Answer 15

Question 16

What happens once we have bilirubin?

Answer 16

• Released to bloodstream.
• Free/unconjugated/indirect BR insoluble
• so bound to albumin
• BR/albumin transport to liver

Question 17

what assists uptake of BR in hepatic tissue?

Answer 17

protein carrier

Question 18

what happens to Bilirubin in the liver?

Answer 18

UDP- glucuronate and bilirubin ix go to

bilirubin-monoglucuronide (direct)

via UDP-glucuronyltransferase

another UDP-glucuronate is added to this with same enzyme making

bilirubin-diglucuronide (direct)

Question 19

are bilirubin mono and di- glucuonide indirect?

Answer 19

no they are direct or conjugated and are now soluble

(conjugated with glucuronic acid)

Question 20

UDP-glucuronate formation

Answer 20

UDP-glucose converted UDP-glucuronic acid

via UDP glucuse dehydrogensase

Question 21

Bilirubin-diglucuronide in liver then does what?

Answer 21

moves to the gallbladder (part of bile)

Question 22

From gallbladder what happens (Path 1)

Answer 22

bilirubin-diglucuronide goes to bilirubin

bilirubin goes to urobilinogen

via microbial reduction

Urobilinogen gets reabsorb to kidneys

goes to urobilin (yellow color of urine)

Question 23

From gallbladder what happens (path two)

Answer 23

bilirubin-diglucuronide goes to bilirubin

bilirubin goes to urobilinogen

via microbial reduction

urobilinogen goes under further microbial reduction to red-brown stercobilin (feces color)

Question 24

Jaundice

Answer 24

hyperbilirubinemia

elevated levels of BR in blood stream

unconjugated/indirect (.2-.9)

conjugated/direct (.1-.3)

imbalance between production and exrecretion

Question 25

types of jaundice

Answer 25

pre-hepatic intra-hepatic post-hepatic

Question 26

Pre-hepatic jaundice (causes)

Answer 26

increased production of unconjugated BR * excess hemolysis (hemolytic anemias) * internal hemorrhage * liver capacity (uptake, conjugate, excrete) * glucose 6 PO4 dehydrog defic * incompatibility of maternal-fetal blood groups

Question 27

pre-hepatic findings

Answer 27

elevated blood levels unconj or indirect BR normal conjugated BR normal alanine aminotransferase (ALT) and aspartate aminotransferase AST urobilinogen in urine (conjugate not impaired) direct BR absent in urine

Question 28

Intra-hepatic causes

Answer 28

impaired hepatic uptake, conjugation, or secreition of conjugated BR * Hepatic dysfunction * liver cirrhosis * viral hepatitis * **criggler-najjar syndrome** * **Gilbert syndrome**

Question 29

Intra-hepatic findings

Answer 29

* variable increases in unconjugated and conjugated BR depending on the cause (pre post conjugation) * increse in ALT AST in serum (hepatic dysfun) * urobilinogen levels normal * conjugated BR detected in urine

Question 30

Post-hepatic causes

Answer 30

problems with BR excretion AKA cholestatic jaundice (decrease bile flow) obstruct liver of bile duct gall stone carcinoma liver disease lesions drugs

Question 31

Post-hepatic findings

Answer 31

elevated blood levels of conjugated BR small increase in unconjugated form Normal AST ALT elevated ALP conjugated BR in urine (dark) no urobilinogen in urine no stercobilin in feces (pale stool)

Question 32

Neonatal jaundice

Answer 32

Question 33

Phototherapy and neonatal jaundice

Answer 33

Question 34

crigler-Najjar syndrome

Answer 34

(type 1) deficiency of UDP-GT complete absence of gene BR accumulate in brain of babies (serious) * blood transfustions * phototherapy * heme oxygenase inhibitors * calcuim phosphate and carbonate (complex in gut * liver transplant

Question 35

criggler-Najjar syndrome type II

Answer 35

benign form mutation in UDP-GT gene 10% activity (not as severe)

Question 36

Gilbert syndrome

Answer 36

relatively common reduced activity UDP-GT (25%) BR \<6mg/dL may icrease with fasting, stress or alcohol consumption

Question 37

Hepatitis

Answer 37

inflammation of liver (liver dysfunction) viral infec, alcohol cirrhosis, liver cancer * increased levels of unconj and conj BR * BR accum in skin and sclera yellow discolor * tea colored urine

Question 38

Bruises and their colors

Answer 38

breakdown of hemoglobin diff colors * Hemoglobin * heme-red * biliverdin-green * bilirubin-orange * iron-reddish brown (hemosiderin)