Heme Synthesis and Degradation

Question 1

Structure of heme

Answer 1

pyrrole (5 member ring) molecule and atom of Fe in the center of the porphyrin ring (a tetra pyrrole structure). In the order of MVMVMPPM

Question 2

Porphyrin

Answer 2

oxidized tetrapyrrole, highly photoreactive and give off free oxygen radicals when exposed to light

Question 3

Protoporphyrin IX

Answer 3

isomer in heme. consists of 4 methyl groups, 2 vinyl groups, 2 propionate groups, and a tetrapyrrole

Question 4

Heme

Answer 4

protoporphyrin IX chelated with iron (Fe 2+)

Question 5

Hemin

Answer 5

protoporphyrin IX chelated with iron (Fe 3+)

Question 6

Glycine + Succincyl CoA to ALA

Answer 6

Enzyme is ALA synthase, Cofactor is pyridoxal phosphate, Located in Mitochondria

Question 7

ALA + ALA to Porphobilinogen (PBG)

Answer 7

Enzyme is ALA dehydrase, Inhibited by lead, Located in Cytosol, Contains Zn-cofactor that can be replaced with lead

Question 8

Lead poisoning

Answer 8

Lead blocks heme synthesis at two steps. It inhibits porphobilinogen synthase (2nd step) and ferrochelatase (last step). Inhibition of heme synthesis leading to a chronic porphyria. Accumulation of ALA.

Question 9

PBG + PBG+ PBG + PBG to Uroporphyrinogen

Answer 9

Enzymes: PBG deaminase (4 PBG to Uroporphyrinogen 1), Uroporphyrinogen 3 cosynthase (Uroporphyrinogen 1 to Uroporphyrinogen 3). Located in cytosol.

Question 10

Uroporphyrinogen 3 to Protoporphyrin 9

Answer 10

Enzymes: Uroporphyrinogen decarboxylase, Coproporphyrinogen oxidase, Protoporphyrinogen oxidase, Located in cytosol and mitochondrial matrix

Question 11

Protoporphyrin 9 to Protoheme 9

Answer 11

Enzyme is ferrochelatase, Located in Mitochondria

Question 12

Where is heme synthesized?

Answer 12

Liver and Erythroid cells

Question 13

Cytochrome P450

Answer 13

oxidative enzymes involved in detoxification

Question 14

Regulation of heme synthesis in liver cells

Answer 14

Main target is ALA synthase. Heme synthesis can also be induced by toxins or substances that induce cytochrome P450.

Feedback inhibited by heme through: 1. Repression of mRNA synthesis, 2. Inhibition of translation of the ALA synthase mRNA, 3. Inhibition of import of the ALA synthase protein into mitochondria, 4. Direct inhibition of the ALA synthase enzyme.

Question 15

Regulation of heme synthesis in erythroid cells

Answer 15

Heme stimulates the synthesis of enzymes in the heme biosynthetic pathway

Question 16

Congenital erythropoietic porphyria

Answer 16

deficiency in uroporphyrinogen 3 co-synthase. accumulation of uroporphyrinogen 1 and coproporphyrinogen 1, anemia, skin is photosensitive, red urine, increased hair growth (Erythroid cells)

Question 17

Protoporphyria

Answer 17

partial deficiency in ferrochelatase, mild version of congenital erythropoietic porphyria (Erythroid cells)

Question 18

Acute intermittent porphyria

Answer 18

partial deficiency of porphobilinogen (PBG) deaminase. Accumulation of ALA and PBG. Influenced by diet. (Liver)

Question 19

Porphyria cutanea tarda

Answer 19

deficiency in uroporphyrinogen decarboxylase (Liver)

Question 20

Haptoglobin

Answer 20

Binds methemoglobin dimers (hemoglobin with iron in the ferric state)

Question 21

Hemepexin

Answer 21

Binds free heme

Question 22

Transferrin

Answer 22

Binds free iron

Question 23

Reticular Endothelial Cells in Spleen

Answer 23

Phagocytize aging red blood cells.

Question 24

Heme to Biliverdin

Answer 24

Enzymes: Heme oxygenase, Located in Spleen

Question 25

Biliverdin to Bilirubin

Answer 25

Enzyme: Biliverdin reductase, Located in Spleen

Question 26

Conjugation of Bilirubin

Answer 26

Enzyme: Glucuronyl bilirubin transferase, Located in Liver

Question 27

Crigler-Najjar Syndrome

Answer 27

Deficiency in UDP-glucuronyl transferase and results in severe jaundice

Question 28

Neonatal Jaundice

Answer 28

insufficient levels of UDP-glucuronyl transferase by the infant

Question 29

Conjugated Bilirubin to Urobilinogen

Answer 29

Converted by intestinal bacteria in the gut.

Question 30

Urobilin

Answer 30

Oxidation of urobilinogen. Contributes ot the color of normal urine and feces

Question 31

Coproporphyrinogen 3

Answer 31

last precursor in heme synthesis with solubility, defects down pathway results in accumulation