Heme

Question 1

Heme users

Answer 1

All cells that use oxygen need heme, tissue specific reg and synth, any complete block of heme is death

Question 2

Loc of heme synth

Answer 2

Most made in RBCs so heme made where RBCs made
Fetal =yolk to liver
Neonate = spleen
Adult = bone marrow

Question 3

Draw heme synth pathway

Answer 3

Paper

Question 4

Heme synth step 1

Answer 4

Succinyl CoA and glycine to delta-ALA (x2)
enzyme = delta-ALA synthase
rqrs PLP

Question 5

Heme synth step 2

Answer 5

2 delta-ALA to porphobilinogen
rxn x4 to 4 porphs
enz = delta-ALA dehydratase
rqrs Zn (plubism can inhib Zn)

Question 6

Heme synth step 3

Answer 6

4 porphobilinogens to hydroxymethylbilane

Enz = porphobilinogen deaminase

Question 7

Heme synth step 4

Answer 7

hydroxymethylbilane cyclizes to uroporphyrinogen 3

Enz = Uroporphyrinogen 3 cosynthase

Question 8

Heme synth step 5

Answer 8

Uroporphyrinogen 3 to Coproporphyrinogen 3

Enz = Uroporphyrinogen decarboxylase

Question 9

Heme synth step 6

Answer 9

Coproporphyrinogen 3 oxidized to Protoporphyrinogen 9

Enz = coproporphrinogen Oxidase

Question 10

Heme synth step 7

Answer 10

Protoporphyrinogen 9 oxidized to protoporphyrin 9

Enz= portoporphyrinogen Oxidase

Question 11

Heme synth step 8

Answer 11

Iron (Fe2) and protoporphyrin 9 combine to heme
Enz = ferrochelatase
Plubism inhibs iron

Question 12

Heme Synth Reg

Answer 12

Erythropoietic Tissue (BM) - controled by iron availability, makes heme at full capacity

Non-erythro tissue (liver) ALA synthase regulated allosterically by heme (neg feedback) and by hemin/hematin (hemin is heme with iron-3 which inhibs ALA synthase, promotes excretion to porphyrin precursors and heme degrade)

Question 13

Heme degrade step 1

Answer 13

Degraded to biliverdin, CO and Iron-3
Enz = Heme oxygenase
Rqrs Oxygen and NADPH
In macrophages

Question 14

Heme degrade step 2

Answer 14

Biliverdin to Bilirubin
Enz = Biliverdin reductase
Rqrs NADPH, also in macro
*Both bili’s are inhib of lipid peroxidation

Question 15

Heme degrade step 3

Answer 15

Bilirubin to blood (albumin) to liver
conjugates with 2 glucoronates (from UDP-glucouronate from glucose) to bilirubin diglucoronide
Enz =bilirubin glucoronyl transferase
Conjugates bilirubin to bile

Question 16

Heme degrade step 4

Answer 16

Once with bile it goes to SI where bact convert to urobilinogen
Goes to urine as urobilin (yellow) or stays in gut to oxidize to sterobilin (brown poo)

Question 17

Porphyrias gen

Answer 17

Usually autodominant (except congenital Eryth Porphyria = AR), most common = Porphyria Cutanea Tarda
Always decreases heme synth
Any step after porphobilinogen is photophobic

Question 18

Acute Intermittent Porphyria

Answer 18

no photosensitivity
Mutation in porphobilinogen deaminase (hydroxymethylbilane synthase)
Leads to prevention of polymer asembly

Question 19

Congenital Erythropoietic Porphyria

Answer 19

AR
Mutation in Uroporphyrinogen 3 cosynthase leading to accumulation of hydroxymethylbilane
Phototoxic and photosensitive since hydroxymethybilane is a conjugated molecule which can form radicals

Question 20

Treatment of Porphyrias

Answer 20

Admin heme/hematin, avoid direct sunlight, Ingest beta carotene (Vit A)

Question 21

Dubin Johnson Syndrome

Answer 21

Mutations in bilirubin glucoronyl transferase, AR

Black liver and hyperbiliruinemia

Question 22

Jaundice

Answer 22

Overproduction of bilirubin or hepatic failure

Question 23

Hemolytic Jaundice

Answer 23

Massive amount of RBC lysis (malaria/sickle) exceeds liver capacities to degrade bilirubin

Question 24

Neonatal jaundice

Answer 24

decreased bilirubin glucornyl transferase leads to build up of unconj bilirubin and mimics hepatic failure
Treat with UV and Vit B2 (riboflavin)

Question 25

Obstructive Jaundice

Answer 25

Obstruction of bile duct due to stone or tumor leads to back up of bilirubin in blood and liver leading to excretion in urine

Question 26

Hepatocellular Jaundice

Answer 26

Cirrhosis, shows urine as very dark