Hemoglobin Synthesis

Question 1

Composition of porphyrin ring

Answer 1

Four pyrrole rings

Question 2

Structure of heme

Answer 2

Heme molecule in the center of a porphyrin ring with side chain groups MVMVMPPM

Question 3

Methyl

Answer 3

CH3

Question 4

Vinyl

Answer 4

CH=CH2

Question 5

Propionate

Answer 5

CH2-CH2-COOH

Question 6

Protoporphyrin IX chelated with iron

Answer 6

Heme

Question 7

Heme a

Answer 7

Modification of the number 2 vinyl group

Question 8

Heme b

Answer 8

Normal heme

Question 9

Heme c

Answer 9

Covalently bound to cysteine residues of proteins through the two vinyl groups

Question 10

Biosynthetic pathway steps

Answer 10

1. ALA synthesis from glycine and succinyl CoA
2. Porphobilinogen
3. Uroporphyrinogen
4. Protoporphyrin
5. Protoheme IX (heme)

Question 11

Aminolevulinate synthase (ALAS)

Answer 11

ALA sythesis from glycine and succinyl CoA. Requires cofactor pyridoxal phosphate

Question 12

ALA synthesis loaction

Answer 12

Mitochondria

Question 13

Porphobilinogen synthase (ALA dehydrase)

Answer 13

Synthesises porphobilinogen from 2 ALA. Inhibited by lead.

Question 14

Porphobilinogen synthesis loaction

Answer 14

Cytosol

Question 15

Uroporphyrinogen synthase (PBG deaminase)

Answer 15

Catalyzes condensation of four substrate molecules and the subsequent cyclization to form the tetrapyrrole ring, uroporphyrinogen I. Releases 4 NH3 groups.

Question 16

Uroporphyrinogen III cosynthase

Answer 16

Catalyzes the isomerization reaction to yield uroporphyrinogen III. Flips the D ring into the correct orientation.

Question 17

Uroporphyrinogen synthesis location

Answer 17

Cytosol

Question 18

Uroporphyrinogen decarboxylase

Answer 18

Catalyzes the decarboxylation of four acetyl side chains of uroporphyrinogen III to methyl groups to form coproporphyrinogen III.

Located in cytosol.

Question 19

Coproporphyrinogen oxidase

Answer 19

Catalyzes the decarboxylation of two propionyl side chains to vinyl groups to form protoporphyrinogen IX.

Located in matrix.

Question 20

Protoporphyrinogen oxidase

Answer 20

Removes six hydrogen atoms to form protoporphyrin IX.

Located in matrix.

Question 21

Ferrochelatase

Answer 21

Inserts iron into protoporphyrin IX.

Inhibited by lead.

Located in mitochondria.

Question 22

Cytochrome P450

Answer 22

Oxidative enzymes that contain heme involved in detoxification in the liver

Question 23

Two sites of heme biosynthesis

Answer 23

Liver and erythroid cells

Question 24

Regulation of heme synthesis in liver cells

Answer 24

Targets the first step–ALA synthase.
Potential pathways: Repression of mRNA synthesis, inhibition of translation of the ALA synthase mRNA, inhibition of the ALA synthase protein into mitochondria, direct inhibition of the enzyme.

Question 25

Porphyrias

Answer 25

Genetic deficiencies in heme metabolism. Hepatic and erythropoietic.

Question 26

Congenital erythropoietic porphyria

Answer 26

Deficiency in uroporphyrinogen III co-synthase. Autosomal recessive trait. Causes accumulation of uroporphyrinogen I and coproporphyrinogen I. Skin is photosensitive.

Question 27

Protoporphyria

Answer 27

Partial deficiency in ferrochelatase. Autosomal dominant. Similar symptoms to CEP.

Question 28

Acute intermittent porphyria

Answer 28

Partial deficiency of porphobilinogen (PBG) deaminase. Autosomal dominant or haploinsufficiency. Acute attacks brought on by substances. Accumulation ALA and porphobilinogen.

Question 29

Porphyria cutanea tarda

Answer 29

Deficiency in uroporphyrinogen decarboxylase. Sporatic or autosomal dominant. Asymptomatic until liver disease in imposed.