Heme Flashcards
Carbon Monoxide Poisoning
Carbon monoxide binds tightly but reversible to iron hemoglobin.
- replaces oxygen
- traps hemoglobin in relaxed form
how does carbon monoxide poisoning look on a graph?
- shifts saturation curve to HYPERBOLA
- oxygen is not released in tissue
Embryonic Hemoglobin has a higher affinity to oxygen than HbA due to what? and what is the significance of this feature?
weak binding of 2,3 BPG by HbF
-facilitates transfer of oxygen across placenta from mother to fetus
alpha gene family
occurs at chromosome 16 on a single chromosome.
-diploid has 4 copies of 2 active genes.
Beta gene chromosome
occurs at chromosome 11
-1 copy of beta gene and diploid 2 copies.
How does goblin gene expression occur and where?
in RBC precursors
Transcription->
splicing->translation into globin protein
Alpha Hemoglobin stabilizing protein (AHSP)
binds and stabilizes excess alpha hemoglobin
Sickle Cell Disease.
what type of point mutation, AA and location of mutation
autosomal, recessive disorder
- point mutation in beta globin
- GAG to GTG
- leads to a single AA change 6th position of hemoglobin beta protein val to glu
Sickle Cell Disease. What does the HbS fibers do to erythrocte. What is the role of microinfarcts?
HbS form fibers distorting erythrocyte.
- elongated erythocytes occlude blood flow in capillaries.
- microinfarcts produce tissue anoxia resulting in severe pain.
- increase susceptibility to infections, acute chest syndrome, stroke, splenic and renal dysfunction
What is the selective disadvantage of sickle cell disease?
heterozygotes are less susceptible to malaria.
-shorter life span for RBCs prevent P. falciparum from completing its life cycle
Hemoglobin C Disease. where does point mutation occur? what type of AA?
Point mutation in beta globin gene.
-leads to single amino acid change in 6th position of hemoglobin beta protein glu to lys.
What happens to homozygous individuals that have hemoglobin C disease?
- mild, chronic hemolytic anemia.
- No infarctive crises
- no treatment necessary
Hemoglobin SC disease. what happens to beta globin chains?
beta globin chains carry HbS and some carry HbC mutations
methenoglobinemia
contains ferric (3+) instead of ferrous (Fe2+) -methemoglobin can't bind oxygen
in methenoglobinemia what are the causes when methemoglobin can’t bind oxygen?
- oxidation of iron by drugs (nitrates)
- deficiency of NADH-cytochrome B5 reductase
- (NADH methemglobin reductase reduces Fe3+ to Fe2+)
Thalassemias
imbalance in synthesis of globin chain.
-reduced rate of production of one globin
alpha thalassemias
4 alpha globins
-one altered gene for globin (silent)
-2 alter gene: alpha t. trait
-3 altered genes: HbH disease with mild hemolytic anemia
4 altered: hydrops fetaliz: causes fetal death
beta thalassemias
altered expression in thalassemias trait (minor)
2 altered: majpr
What are the storage proteins and what do they carry?
Albumin: carry protein
transferrin: transport ferric iron
ferritin: iron storage protein
Albumin transports
divalent( Ca2+) and trivalent cations (Fe3+)
- hydrophobic molecules: fatty acids, sterols, bilirubin
- drugs: penicilin and warfarin etc.
Hemosiderin
derivative of Ferritin used to store iron in liver, spleen and bone marrow
-insoluble in aq solution
ceruloplasmin
transports copper (Cu2+) liver to peripheral tissue
- regulates iron transport
- increase in cerulosplasmin concentration is observed in liver disease and tissue damage
wilson’s disease
low ceruloplasmin
elevated serum copper
elevated excretion of urine
metabolic defect is in excretion of copper in bile and its reabsorption in kidney
Myoglobin describe the structure and the AA within
- 150 AA
- 8 alpha helixes (a-H)
- AA with NP inside
- AA charged groups at the surface
- bound to Heme
Heme structrue
-protoprophyrin IX and ferrous (Fe 2+) iron
-prosthetic group: non protein factor needed for enzyme activity. covalently attached enzyme
-iron forms 6 bonds
four with N of protoporphyrin
Heme binds with
- one proximal histidine to F helix
- oxygen stabilized by distal histidine
What happens to the structure of hemoglobin when oxygen binds in hemoglobin?
iron moves to plane of hemoglobin
What are the functions of Heme
- carries oxygen of hemoglobin and myoglobin
- carries electrons for redox reactions and cytochrome
- breaks down hydrogen peroxide
Hemoglobin A
carries oxygen, CO2 and protons.
found in RBCs
What is the structure of Hemoglobin? What type of bonds attach to subunits?
heteroteramer:
2 alpha chains,2 beta chains
-subunits attach by hydrophobic interactions
How do alpha and beta dimers interact?
hydrophobic and ionic interaction
-dimers interact through
ionic and hydrogen bonds
Tense or taut form has what type of infinity?
deoxygenated form -low oxygen affinity
Relaxed form
oxygenated form, high oxygen affinity
Hemoglobin exhibits __. What does the term mean? What is the shape of curve
Cooperatively: as one oxygen binds, the affinity for another oxygen is increased.
-sigmodal dissociation curve
Hemogloblins affinity for the 4th oxygen is how many more times than the first 1?
300x
What does the dissociation curve is steepest at the oxygen concentrations that occur in where?
Tissues. allows oxygen delivery to respond to small changes in pO2
Oxygen binding hemoglobin is Allosterically effected by and release of oxygen is enhanced how?
pH: released of oxygen is enhanced by decreasing pH
pCO2:release of Oxygen is enhanced by increase C02
2,3-BPG
2,3-BPG
synthesized from intermediate in glycolysis.
-stabilizes taut form of Hb
What is the Bohr effect and Give example.
increase in [H+] lowers that affinity of hemoglobin for oxygen.
Ex: pH 7.6 in alveoli of lungs has a higher affinity than tissues pH (7.2)
CO2 + H2O -> H2CO3
carbonic anhydrase catalyzes the formation of carbonic acid from carbon dioxide and water.
H2CO3 -> HCO3- + H+
carbonic acid spontaneously dissociates into bicarbonate and a proton.
Some CO2 binds to hemoglobin as___.
carbamate: (carbamino-hemoglobin)
What is the structure for Heme
-Protoporphyrin IX and ferrous (Fe2+) iron
-Prosthetic group
-Iron forms 6 bonds
Four with N of protoporphyrin
Prosthetic group
nonprotein factor needed for enzyme activity
-covalently attached to enzyme (not dissociable)
What is the structure of hemoglobin?
- Its a heterotetramer.
- 2 alpha and 2 beta chains attached by hydrophobic interactions
