Globular Proteins Flashcards
Describe structure of hemoglobin (HbA)
2 alpha subunits, 2 beta subunits
Each have a heme inside which has a Fe2+ inside and an O2 inside each
Oxygen bound hemoglobin
oxyhemoglobin
non oxygen bound hemoglobin
deoxyhemoglobin
CO2 bound hemoglobin
carbaminoglobin
what does Hydrogen bound hemoglobin create?
buffer
function of 2,3 BPG
regulates HbA affinity for Oxygen
binds on B subnunit for hemaglobin to unload Oxygen
Forces Oxygen unloading
CO2 in blood causes
release of ions, increase in acidity, decrease in pH and shift curve to the Right
Working muscle effect on oxygen hemoglobin dissociation curve
Goal is to send oxygen to the muscle (unload from hemoglobin)
decrease in pH, increase temperature, increase carbon dioxide, increase hydrogen concentration, increase 2,3 BPG (unloads Oxygen)
All causes shift right
Bohr effect
Hb affinity for oxygen decreases in tissue as there is an increase of CO2
Haldane effect
Hb affinity for CO2 decreases in lungs as increase in Oxygen
What does a left shift on the oxygen hemoglobin dissociation curve correlate to ?
higher affinity for oxygen
Does not want to let go
Fetal hemoglobin
much higher affinity for oxygen
alpha and gamma subunits
How to treat sickle cell disease?
gamma subunit of fetal hemaglobin injected, induce changes to blood from mutated B subunit
Myoglobin
No cooperativity in curve (one subunit)
final oxygen reserve for muscle, making it a high affinity for oxygen
globular protein characteristics
spherical, water soluble, catalytic/reg/transport in metabolic function
often contain heme
Myoglobin function
transport and store oxygen in skeletal and cardiac muscle cells
hemoglobin function
transport oxygen, carbon dioxide, and hydrogen ions in red blood cells
Structure of heme
4 rings goes from MP, MP, MP to PM (D ring shows orientation)
Heme, CO and O2
CO much stronger in binding heme, creating asphyxiation
Overtime the CO binding weakens as is bent and allows Oxygen recovery
Hemoglobin quarternary structure
between alpha and beta subunits, has hydrophobic interactions
Between dimers has polar bonds
T form hemoglobin
tense, deoxygenated, tightly packed form with H bonds between dimers
R form hemoglobin
relaxed, oxygenated, allow oxygen to enter with high affinity, poalr bonds rupture bewteeen dimers
allosteric effects on the oxygen dissociation curve
partial pressure of Oxygen
pH
partial pressure of CO2
2,3 BPG
temperature
Effect of CO2 in hemoglobin
10% carry as carbamate on Nterminal groups
can create T form of Hb and lead to right shift of curve as wants to offload oxygen
binding of CO in hemoglobin
binds to Fe in heme shifting to R state making the tissue unable to release oxygen
what chromosomes are important for organization of globin genes?
11 & 16
hemoglobinopathies causes
decrease production of normal globin proteins
abnormal structure of one of globin chains of Hb molecule (decrease ability to bind oxygen)
Hemoglobin S disease
HbS
red cell sickling, hemolytic anemia
Glutamic acid to valine
Screen in alkaline pH as migrate more slowly
Hemoglobin C disease
HbC is variant of glutamic acid to lysine at position 6 of Beta chain
Hemoglobin SC disease
compound of heterozygotes
significant red cell sickling
methemoglobinemia
higher than normal level of methemoglobin
changes ferrous to ferric and decerases oxygen affinity
Hepcidin
major regulator of ferroportin (exports Fe2+)
important steps iron absorbtion
export of ferrous iron by ferroportin
oxidation of ferrous iron to ferric iron
load ferric iron onto transferrin
clear ferroportin from membrane by hepcidin
Transferrin receptor (TfR1)
transmembrane glycoprotein
expresion incresaes when iron levels are low
allows Fe to enter cell
iron deficiency anemia
microcytic hypochromic anemia
from chronic bleeding, malnutrition, or absorbtion disorder
