porphyrins and hemoglobin Flashcards
describe the structure of porphyrins
cyclic structure of 4 pyrrole rings joined by methine bridges
define heme
the prosthetic group of hemoglobin responsible for binding oxygen
define porphyrias
a group of rare disorders tht result from disturbances in heme synthesis
define porphyrins
chemical intermediates in synthesis of hemoglobin, myoglobin and other respiratory cytochromes
- oxidized product of porphyrinogens
define porphyrinogens
reduced compounds that are intermediates in biosynthesis of heme
- oxidized to porphyrins
describe porphyrinogen isomers
substitutions in pyrrole ring
-> 4 kinds but ONLY type 3 makes heme
describe aqueous solubility of porphyrins
vary with amount of carboxylic acids present (more = more soluble)
list Uroporphyrin, coproporphyrin and porphyrins in order of solubility
(most) uroporphyrin - 8 groups (found in urine)
Coproporphyrin - 4 groups
(least) porphyrin - 2 groups (not found in urine)
true or false
all cells contain hemoproteins and can synthesize heme
true
how many enzymes are necessary in sequence of heme reactions
8 different enzymes
how many molecules of ALA are needed to form one molecule of heme
8 ALA makes 1 heme
which steps of heme synthesis take place in mitochondria
first and last 3
-> highest energy demand
describe the final step in heme synthesis
ferrochelatase adds ferrous (Fe2) iron into protoporphyrin to form heme
which enzyme is regulated in heme synthesis in the negative feedback loop
ALA synthase
how are disorders of heme biosynthesis grouped
based on clinical manifestations
- cutaneous
- neurological
- neurocutaneous
describe neuropsychiatric disorder of heme synthesis
- excess of early precursors in synthesis (ALA and PBG)
list neuropsychiatric porphyrias
- ALA dehydratase deficiency porphyria (ADP)
- Acute intermittent porphyria (AIP)
describe cutaneous porphyria’s
photosensitivity, blisters etc
excess of porphyrin intermediates
- chronic conditions
list cutaneous porphyias
- Congenital erythropoietic porphyria (CEP)
- Porphyria cutanea tarda (PCT)
- Erythropoietic protoporphyria (EPP)
- X linked protoporphyria (XLPP)
which porphyrias are related to increased fragility of light exposed skin
Cutaneous -> CEP and PCT
which porphyrias are related to bruning of light exposed skin
Cutaneous -> EPP and XLPP
describe neurocutaneous porphyria symptoms
both neuro (abdominal pain/nausea) and cutaneous (burning of skin)
- build up of both early precursors and porphyrin intermediates
list neurocutaneous porphyrias
- hereditary coproporphyria (HCP)
- Variegate porphyria (VP)
-> can be acute porphyria)
describe acute porphyrias
conditions with neurological symptoms and acute attacks
- ADP and AIP (neuropsychiatric)
- HCP and VP (neurocutaneous)
-> AIP most common
describe secondary porphyrinurias
acquired condition with increased urinary porphyrin
- liver disease and lead most common
define hemoglobinopathies
defects in hemoglobin structure
- amino acid substitutions most common
- hgb S, C, SC etc
define thalassemias
defects in rate and quantity of production
where is alpha globin chain gene located
chromosome 16
where are beta, gamma and epsilon globin chain genes located
chromosome 11
which hemoglobinopathies result from fused or hybrid chains
lepore (delta beta)
kenya (gamma beta)
list the subgroups of hemoglobinopathies
- substitution
- deletion
- mutation
- fused/hybrid
where does globin and heme synthesis take place
- globin = cytoplasm
- heme = mitochondria
describe hemoglobin S
- 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
describe hemoglobin C
- hemoglobinopathy
- 6th pos on beta chain glutamic acid switched for lysine => overall positive charge
- crystal cells
- cellulose acetate alkaline hgb electrophoresis
describe hgb SC
- 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
describe hgb E
- hemoglobinopathy
- glutamic acid switched for lysine 26th pos
- cellulose acetate first
- confirmed on citrate (migrates with A)
describe hgb D
- glutamic acid switched for glycine
- alkaline then acidic hgb electrophoresis
list order of electrophretic mobility of hgb S, C, F and A
(slow) C
S
F
(fastest) A
what is the definitive tst for hemoglobinopathies and thalassemias
DNA analysis
list the utility for testing myoglobin
- rhabdomyolysis
- myocardial infarction
- hereditary progressive muscular dystrophy
