Porphyrins & Bile Pigments

Question 1

Bilirubin to bilirubinglucoronide

Answer 1

UDP glucoronyl transferase

Question 2

Two (2) rxns of heme oxygenase system

Answer 2

(1) Iron is oxidized to ferric form (Fe3+) - HEMIN

(2) Hemin is reduced to HEME

Question 3

Transports bilirubin to liver

Answer 3

Plasma albumin

Question 4

Heme + heme oxygenase forms what?

Answer 4

Oxy-heme (closed tetrapyrrolic ring with iron)

Question 5

Oxy-heme + heme reductase forms what?

Answer 5

Biliverdin (open tetrapyrrolic ring without iron)

Question 6

Biliverdin + biliverdin reductase forms what?

Answer 6

Bilirubin (unconjugated, lipophilic)

Question 7

Type of transport system in hepatocellular uptake of bilirubin

Answer 7

Facilitated transport system (carrier-mediated)

Question 8

Intracellular transport of bilirubin in hepatocytes: Group of enzymes that represent 2% of cytosolic proteins

Answer 8

Ligandins

Question 9

Intracellular transport of bilirubin in hepatocytes: Proteins that bind fatty acids

Answer 9

Z Protein

Question 10

Three (3) sugars used in conjugation of bilirubin with glucoronic acid

Answer 10

Glucose (cell sap),
Xylose & Glucuronic Acid (formed from glucose by UDP-glucose)

Other agents eliminated by conjugation with glucuronic acid:
Steroids, thyroid hormones, catecholamines, estradiol, testosterone, bile acids, phenols, morphine

Question 11

Enzyme in 1st step of glucuronidation of bile (glucose + ______ = UDPGA)

Answer 11

UDP-glucose dehydrogenase

Question 12

Enzyme in 2nd step of glucuronidation of bile

Answer 12

Bilirubin-DUGAN-transferase (synthesized by microsomes)

Question 13

Drugs that favor bilirubin conjugation and elimination

Answer 13

Phenobarbital, Antipyrine (microsomal enzyme inducers)

MOA: Increase bilirubin transferase activity

Question 14

UDPGA + bilirubin + glucuronyl transferase = _______

Answer 14

Bilirubin mono- and di-glucuronides

Question 15

Secondary to increased bilirubin (unconjugated) levels in the blood

Answer 15

Icterus/Icterisia (jaundice)

Elevated amts of conjugated bilirubin - obstructs biliary tree

Question 16

Bilirubin conjugation/excretion capacity of liver

Answer 16

3000 mg per day (normal pdn of 300 per day)

Question 17

Type of jaundice associated with:
Sickle cell anemia,
Pyruvate kinase deficiency,
Glucose-6-phosphate deficiency,
Malaria

Answer 17

Hemolytic jaundice

Question 18

Type of jaundice associated with:
Hepatic tumor,
Bile stones,
Biliary atresia

Answer 18

Obstructive jaundice (pale-colored stools)

Question 19

Type of jaundice presenting with elevated SGOT (AST) and SGPT (ALT)

Answer 19

Hepatocellular jaundice

Question 20

Enzyme associated with physiologic jaundice of the newborn

Answer 20

Hepatic bilirubin glucuronyl transferase (low levels at birth)

Question 21

Occurs when elevated bilirubin levels exceeding the binding capacity of albumin and deposit into basal ganglia

Answer 21

Kernicterus (toxic encephalopathy)

Question 22

MOA of phototherapy in jaundice (newborns)

Answer 22

Conversion of bilirubin to more polar, water-sol isomers (excreted into bile without conjugation to glucuronic acid)

Question 23

Mg-containing porphyrin

Answer 23

Chlorophyll

Question 24

Type I Porphyrin

Answer 24

Symmetric substitution

Question 25

Type III Porphyrin

Answer 25

Asymmetric substitution

Question 26

Porphyrin linkage: 4 pyrrole rings through ____ or ____

Answer 26

Methyne or methenyl bridges

Question 27

Heme is synthesized from

Answer 27

Porphyrins and iron

Question 28

Heme is degraded into

Answer 28

Bile pigments and iron

Question 29

Gives red color to heme

Answer 29

Protoporphyrin

Question 30

Colorless compounds

Answer 30

Porphyrinogens

Question 31

Responsible for absorption and fluorescence in porphyrins

Answer 31

Double bonds joining pyrrole rings

Question 32

ALA dehydratase deficiency

Answer 32

ALA dehydratase-deficiency porphyria

Question 33

PBG deaminase deficiency

Answer 33

Acute intermittent porphyria - Most commonly occurring porphyria - Enzyme also called UPG synthase or hydroxymethylbilane synthase

Question 34

Uroporphyrinogen III synthase deficiency

Answer 34

Congenital erythropoietic porphyria (CEP) - Recessive

Question 35

Uroporphyrinogen decarboxylase deficiency

Answer 35

Porphyria cutanea tarda

Question 36

Coproporphyrinogen oxidase deficiency

Answer 36

Hereditary coproporphyria

Question 37

Protoporphyrinogen oxidase deficiency

Answer 37

Variegate porphyria

Question 38

Ferrochelatase deficiency

Answer 38

Protoporphyria

Question 39

Rate-controlling enzyme in heme synthesis

Answer 39

ALA synthase (d-aminolevulinic acid synthase)

Question 40

d-aminolevulinate formed from condensation of what substrates?

Answer 40

Succinyl-CoA and Glycine - ALA synthase enzyme - 1st rxn in heme synthesis

Question 41

Dimerization reaction between two (2) d-aminolevulinate molecules and catalyzed by ______ forming ______ and ______

Answer 41

Enzyme: ALA dehydratase (Zn-containing) Product: Porphobilinogen, H2O - ALA dehydratase OR PBG synthase OR hydroxymethylbilane synthase - 2nd rxn in heme synthesis

Question 42

Enzymes catalyzing these condensation rxn: (A) Porphobilinogen + H2O = hydroxymethylbilane (B) Hydroxymethylbilane to uroporphyrinogen I (C) Hydroxymethylbilane to uroporphyrinogen III

Answer 42

A. Uroporphyrinogen I synthase (PBG deaminase) B. NONE; Non-enzymatic C. Uroporphyrinogen III synthase + protein uroporphyrinogen II cosynthase - 3rd rxn in heme synthesis

Question 43

Uroporphyrinogen III to Coproporphyrinogen III, releasing CO2 (4 mol)

Answer 43

Uroporphyrinogen decarboxylase - decarboxylation rxn (acetate grps of UPG III to methyl) - 4th rxn in heme synthesis

Question 44

Coproporphyrinogen III to Protoporphyrinogen IX

Answer 44

Coproporphyrinogen III oxidase - requires O2 - only acts on Type III - decarboxylation and oxidation of 2 proprionate residues - 5th rxn in heme synthesis (mitochondria)

Question 45

Protoporphyrinogen IX to Protoporphyrin IX

Answer 45

Proptoporphyrinogen III oxidase - requires molecular O2 - oxidation rxn - 6th rxn in heme synthesis (mitochondria)

Question 46

Protoporphyrin IX to heme

Answer 46

Ferrochelatase OR heme synthase - insertion of iron into ring system - 7th rxn in heme synthesis (mitochondria)

Question 47

Important for detoxification

Answer 47

Hepatocytes

Question 48

Hepatic or erythroid? A. ALA Synthase 1 B. ALA Synthase 2

Answer 48

1. Hepatic - ALAS 1 | 2. Erythroid - ALAS 2

Question 49

Prevents ALAS 1 activity

Answer 49

Glucose and hemin

Question 50

Rate of heme synthesis (inc/dec) with diminished intracellular heme concentration and (high/low) levels of ALAS 1

Answer 50

Increases; Low

Question 51

Feedback inhibitor on ALA synthase

Answer 51

Hemin - Inhibits transport of ALAS from cytosol to mitochondria - Represses synthesis

Question 52

Characteristic absorption spectrum band in all porphyrins

Answer 52

Soret band

Question 53

Increased excretion of ____ and ____ in porphyrias

Answer 53

Coproporphyrins | Uroporphyrins

Question 54

Heme synthesis products measured in urine through spectrophotometry

Answer 54

ALA and PBG

Question 55

Three (3) treatments for porphyria

Answer 55

Glucose loading Hematin Beta-carotene

Question 56

Bilirubin conjugation

Answer 56

UDP glucoronyl transferase

Question 57

Biliverdin color

Answer 57

Blue green

Question 58

Colorless porphyrin

Answer 58

Urobilinogen

Question 59

Color of feces d/t

Answer 59

Stercobilin

Question 60

Only rxn in body to produce CO

Answer 60

Heme oxidation