Hemoglobin and Myoglobin Flashcards
where in the body does Hb bind O2
- in the alveoli of the lungs
where in the body does Hb deliver O2
- to tissues throughout the body
how does Hb assist in maintaining acid-base balance in the body
- binding some CO2 produced by metabolism
- releasing CO2 when Hb reaches the lungs
function of Hb dependent upon
- partial pressure gradients of O2 or CO2
partial pressure of a gas equal to
atmospheric pressure x fraction of atmosphere composed of that gas
significance of different of partial pressure between lungs, tissues, and blood
- driving force for gas exchange
myoglobin synthesized where
- inside muscle cells
- skeletal muscle, smooth muscle, cardiac muscle
function of myoglobin
- stores oxygen in muscle cells for use at times of high metabolic demand
myoglobin content varies by
- skeletal muscle fiber type
- IA > IIA > IIB
percentage and type of helix found in myoglobin
- 80% alpha helical
order of structure in myoglobin
- closely packed tertiary structure
heme in structure of myoglobin
- single heme molecule covalently bound
myoglobin binding of oxygen
- binds one O2 molecule at heme
molecule on inside of heme ring
- Fe2+
heme ring hydrophobic or hydrophilic
- hydrophobic
polypeptide chains hemoglobin
- 2 alpha
- 2 beta
polypeptide chain in myoglobin
- single polypeptide chain
amount of O2 bound by hemoglobin
- can bind 4O2 at once
hemoglobin interactions between subunits
- strong hydrophobic interactions between alpha 1 and beta 1
- and alpha 2 and beta 2
- weaker polar interactions between a1B1 and a2B2
HbA composition
- a2B2
- quaternary higher order conformation
significance of HbA
- glycosylation is marker for chronically elevated blood sugar
HbA2 composition
- a2 delta 2
HbF composition
- a2y2
thalassemias
- imbalance in globin chain synthesis
what forms coordinate covalent bonds to Fe2+ in heme
- pyrrole rings
purpose of hydrophobic chains from pyrrole rings
- interact with a/B globin chains to stabilize heme binding
class of pigments that heme belongs to
- porphyrins
binding curve of myoglobin
- hyperbolic
- single constant affinity for O2
P50 of myoglobin
- 2.8 torr
binding curve of hemoglobin
- sigmoidal
- changing affinity for O2 over the binding curve
P50 of hemoglobin
- 26 torr
P50 definition
- the partial pressure of O2 at which 50% of O2 binding sites are occupied
two conformation of Hb
- taught
- relaxed
taught conformation favors which form
- deoxy
- O2 release
relaxed conformation favors which form
- oxy
- O2 binding
O2 regulation of hemoglobin
- affects equilibrium between T and R forms
- positive allosteric regulator of Hb O2 binding
movements of proximal and distal histidines cause
- attached alpha helices to move
- causes conformational change at interface of each aB dimer in the Hb molecule
2,3-DPG on hemoglobin binding curve
- shifts right
2,3-DPG acts on hemoglobin
- stabilized T (deoxy) state
- allow Hb-bound-O2 to dissociate and supply O2 to tissues operating at a high metabolic rate
2,3-DPG and hypoxia
- makes O2 release by Hb more responsive to hypoxia
- allows more O2 release at low pO2
physiological changes that cause change in 2,3-DPG levels
- COPD
- high altitude
- chronic anemia
- pregnancy
Haldane effect
- high pO2 increases binding of O2 to Hb
- less binding of H+ and CO2
- O2 is affecting the affinity of Hb for CO2/H+
- more CO2 delivery to the lungs from tissues
Bohr Effect
- high CO2 and high protons
- protons (due to lower pH) in RBCs bind to Hb
- favor T state, favoring O2 release to the tissues
- CO2/H+ are affecting the affinity of Hb for O2
- more O2 release to tissues from lungs
increase in pH favors
- O2 binding
- shifts left
decrease in pH favors
- O2 release
- shifts right
fetal hemoglobin versus adult hemoglobin A
- fetal hemoglobin has a higher affinity for oxygen
HbF and 2,3-DPG
- binds 2,3-DPG very poorly because cavity is not as positively charged
O2 released by maternal HbA
- bound by fetal HbF
- transported to fetal tissue
the most common Hb variant associated with significant pathology in the Us
- B^s variant
- caused by mutation at position 6 of beta globin gene
- changes Glu to Val
individuals homozygous for B^s allele or heterozygous for B^s and B-thalassemia allele
- produce significant amount of HbS
- have sickle cell disease
importance of deoxy HbS
- forms long polymers within the erythrocyte
- shortens lifespan of RBCs
competitors of Hb A at the iron binding site
- cyanide (CN-)
- carbon monoxide (CO)
- nitrogen dioxide (NO2)
- hydrogen sulfide (H2S)
- all inhibit oxygen binding
effect of competitors of HbA on iron
- do not change oxidation status of iron
- remains Fe2+
carboxyhemoglobin
- stable complex of carbon monoxide and heme in Hb
- forms more readily than oxyhemoglobin
importance of electronic environment of distal (O2-binding) side of heme
- prevents oxidation of Fe2+ to Fe3+ by the bound O2
- would result in O2 release
mutations that change any of the 3 amino acids on the distal side of heme result in
- result in hereditary methemoglobinemia
hereditary methemoglobinemia characterized by
- cyanosis
- brown color to blood
hereditary causes of methemoglobinemia
- mutations in PPP, especially G-6-PD deficiency
- mutations in cytochrome b5 reductase
role of glutathione
- normally reduces reactive oxygen species thereby preventing formation of methemoglobin
deficiency of methemoglobinemia may not present until
- challenged by increased levels of activated O2 species
cytochrome b5 reductase importance
- reduces Fe3+ in methemoglobin to Fe2+
