Heme synthesis

Question 1

amino acid used in synthesis of heme

Answer 1

glycine

Question 2

forms aminolevulinic acid (ALA)

Answer 2

succinyl CoA and glycine (mitochondria)

Question 3

forms porphobilinogen

Answer 3

2 ALAs (cytosol)
via ALA dehydratase  aka  prophobilinogen synthase

Question 4

forms hydroxymethylbilane (HMB)

Answer 4

4 prophobilinogen (cytosol)
 via PBG deaminase  aka HMB synthase

Question 5

enzyme required for heme synthesis in liver

Answer 5

ALAS1

Question 6

enzyme required for heme synthesis in erythroid cells

Answer 6

ALAS2

Question 7

how is ALAS1 regulated

Answer 7

by heme accumulation. negative feedback

Question 8

how is ALAS2 regulated

Answer 8

iron availability

Question 9

disease associated with decreased ALAS2

Answer 9

X-linked sideroblastic anemia

Question 10

cofactor for ALA synthase

Answer 10

PLP (B6)

Question 11

drug used for tuberculosis that depletes PLP as a side effect

Answer 11

Isoniazid

Question 12

inhibitor of ALA dehydratase (prophobilinogen synthase)

Answer 12

lead

Question 13

ring closure of HMB is done by which enzyme

Answer 13

uroporphyrinogen III synthase

Question 14

deficient uroporphyrinogen III synthase leads to

Answer 14

spontaneous ring closure of HMB to form red uroporphyrinogen I, followed by coproporphyrinogen I. accumulation of these two causes extreme photosensitivity

Question 15

attaches ferrous ion to protoporphyrin IX

Answer 15

ferrochelatase

Question 16

inhibitor of ferrochelatase

Answer 16

lead

Question 17

forms coproporphyrinogen III from uroporphyrinogen III

Answer 17

uroporphyrinogen decarboxylase

Question 18

deficiency in urophorphyrinogen decarboxylase

Answer 18

PCT (porphyria cutanea tarda)

Question 19

accumulation of urophorphyrinogen with photosensitivity

Answer 19

PCT

Question 20

accumulation of

uroporphyrinogen I & coproporphyrinogen I with photosensitivity

Answer 20

CEP (congenital erythropoietic porphyria)

Question 21

HCP (hereditary coproporphyria) is cause by a deficiency of which enzyme

Answer 21

coprophorphyrinogen III oxidase

Question 22

VP (variegate porphyria) is caused by a deficiency of which enzyme

Answer 22

protoporphyrinogen oxidase

Question 23

chronic disease caused by a deficiency in ferrochelatase

Answer 23

EPP (erythropoietic protoporphyria)

Question 24

urine darkens on exposure to light and air, no photosensitivity, deficient HMB synthase

Answer 24

AIP (acute intermittent porphyria)

Question 25

treatment of AIP

Answer 25

iv glucose or hemin

Question 26

accumulated in patients with AIP

Answer 26

porphobilinogen and ALA