porphyrins and hemoglobin

Question 1

describe the structure of porphyrins

Answer 1

cyclic structure of 4 pyrrole rings joined by methine bridges

Question 2

define heme

Answer 2

the prosthetic group of hemoglobin responsible for binding oxygen

Question 3

define porphyrias

Answer 3

a group of rare disorders tht result from disturbances in heme synthesis

Question 4

define porphyrins

Answer 4

chemical intermediates in synthesis of hemoglobin, myoglobin and other respiratory cytochromes
- oxidized product of porphyrinogens

Question 5

define porphyrinogens

Answer 5

reduced compounds that are intermediates in biosynthesis of heme
- oxidized to porphyrins

Question 6

describe porphyrinogen isomers

Answer 6

substitutions in pyrrole ring
-> 4 kinds but ONLY type 3 makes heme

Question 7

describe aqueous solubility of porphyrins

Answer 7

vary with amount of carboxylic acids present (more = more soluble)

Question 8

list Uroporphyrin, coproporphyrin and porphyrins in order of solubility

Answer 8

(most) uroporphyrin - 8 groups (found in urine)
Coproporphyrin - 4 groups
(least) porphyrin - 2 groups (not found in urine)

Question 9

true or false
all cells contain hemoproteins and can synthesize heme

Answer 9

true

Question 10

how many enzymes are necessary in sequence of heme reactions

Answer 10

8 different enzymes

Question 11

how many molecules of ALA are needed to form one molecule of heme

Answer 11

8 ALA makes 1 heme

Question 12

which steps of heme synthesis take place in mitochondria

Answer 12

first and last 3
-> highest energy demand

Question 13

describe the final step in heme synthesis

Answer 13

ferrochelatase adds ferrous (Fe2) iron into protoporphyrin to form heme

Question 14

which enzyme is regulated in heme synthesis in the negative feedback loop

Answer 14

ALA synthase

Question 15

how are disorders of heme biosynthesis grouped

Answer 15

based on clinical manifestations
- cutaneous
- neurological
- neurocutaneous

Question 16

describe neuropsychiatric disorder of heme synthesis

Answer 16

• excess of early precursors in synthesis (ALA and PBG)

Question 17

list neuropsychiatric porphyrias

Answer 17

• ALA dehydratase deficiency porphyria (ADP)
• Acute intermittent porphyria (AIP)

Question 18

describe cutaneous porphyria’s

Answer 18

photosensitivity, blisters etc
excess of porphyrin intermediates
- chronic conditions

Question 19

list cutaneous porphyias

Answer 19

• Congenital erythropoietic porphyria (CEP)
• Porphyria cutanea tarda (PCT)
• Erythropoietic protoporphyria (EPP)
• X linked protoporphyria (XLPP)

Question 20

which porphyrias are related to increased fragility of light exposed skin

Answer 20

Cutaneous -> CEP and PCT

Question 21

which porphyrias are related to bruning of light exposed skin

Answer 21

Cutaneous -> EPP and XLPP

Question 22

describe neurocutaneous porphyria symptoms

Answer 22

both neuro (abdominal pain/nausea) and cutaneous (burning of skin)
- build up of both early precursors and porphyrin intermediates

Question 23

list neurocutaneous porphyrias

Answer 23

• hereditary coproporphyria (HCP)
• Variegate porphyria (VP)
  -> can be acute porphyria)

Question 24

describe acute porphyrias

Answer 24

conditions with neurological symptoms and acute attacks
- ADP and AIP (neuropsychiatric)
- HCP and VP (neurocutaneous)
-> AIP most common

Question 25

describe secondary porphyrinurias

Answer 25

acquired condition with increased urinary porphyrin - liver disease and lead most common

Question 26

define hemoglobinopathies

Answer 26

defects in hemoglobin structure - amino acid substitutions most common - hgb S, C, SC etc

Question 27

define thalassemias

Answer 27

defects in rate and quantity of production

Question 28

where is alpha globin chain gene located

Answer 28

chromosome 16

Question 29

where are beta, gamma and epsilon globin chain genes located

Answer 29

chromosome 11

Question 30

which hemoglobinopathies result from fused or hybrid chains

Answer 30

lepore (delta beta) kenya (gamma beta)

Question 31

list the subgroups of hemoglobinopathies

Answer 31

- substitution - deletion - mutation - fused/hybrid

Question 32

where does globin and heme synthesis take place

Answer 32

- globin = cytoplasm - heme = mitochondria

Question 33

describe hemoglobin S

Answer 33

- 6th pos in beta chain glutamic acid switched for valine => less negative charge on cell - solubility test screen - confirmed w/ cellulose acetate alkaline hgb electrophoresis - hemoglobinopathy

Question 34

describe hemoglobin C

Answer 34

- hemoglobinopathy - 6th pos on beta chain glutamic acid switched for lysine => overall positive charge - crystal cells - cellulose acetate alkaline hgb electrophoresis

Question 35

describe hgb SC

Answer 35

- hemoglobinopathy with no normal alpha chain formation (all S or C) - target, sickle and crystal cells - solubility test pos - equal amounts hgb S and C

Question 36

describe hgb E

Answer 36

- hemoglobinopathy - glutamic acid switched for lysine 26th pos - cellulose acetate first - confirmed on citrate (migrates with A)

Question 37

describe hgb D

Answer 37

- glutamic acid switched for glycine - alkaline then acidic hgb electrophoresis

Question 38

list order of electrophretic mobility of hgb S, C, F and A

Answer 38

(slow) C S F (fastest) A

Question 39

what is the definitive tst for hemoglobinopathies and thalassemias

Answer 39

DNA analysis

Question 40

list the utility for testing myoglobin

Answer 40

- rhabdomyolysis - myocardial infarction - hereditary progressive muscular dystrophy