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MCB 2 Block 3 > Heme > Flashcards

Flashcards in Heme Deck (26):
1

Heme users

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

2

Loc of heme synth

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

3

Draw heme synth pathway

Paper

4

Heme synth step 1

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

5

Heme synth step 2

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

6

Heme synth step 3

4 porphobilinogens to hydroxymethylbilane
Enz = porphobilinogen deaminase

7

Heme synth step 4

hydroxymethylbilane cyclizes to uroporphyrinogen 3
Enz = Uroporphyrinogen 3 cosynthase

8

Heme synth step 5

Uroporphyrinogen 3 to Coproporphyrinogen 3
Enz = Uroporphyrinogen decarboxylase

9

Heme synth step 6

Coproporphyrinogen 3 oxidized to Protoporphyrinogen 9
Enz = coproporphrinogen Oxidase

10

Heme synth step 7

Protoporphyrinogen 9 oxidized to protoporphyrin 9
Enz= portoporphyrinogen Oxidase

11

Heme synth step 8

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

12

Heme Synth Reg

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)

13

Heme degrade step 1

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

14

Heme degrade step 2

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

15

Heme degrade step 3

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

16

Heme degrade step 4

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)

17

Porphyrias gen

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

18

Acute Intermittent Porphyria

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

19

Congenital Erythropoietic Porphyria

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

20

Treatment of Porphyrias

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

21

Dubin Johnson Syndrome

Mutations in bilirubin glucoronyl transferase, AR
Black liver and hyperbiliruinemia

22

Jaundice

Overproduction of bilirubin or hepatic failure

23

Hemolytic Jaundice

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

24

Neonatal jaundice

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

25

Obstructive Jaundice

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

26

Hepatocellular Jaundice

Cirrhosis, shows urine as very dark