BIOCHEM Exam 2 Lecture 7
Home > Flashcards > Print Preview
The flashcards below were created by user
on FreezingBlue Flashcards. What would you like to do?
What percentage of protein does myoglobin account for in muscle?
Myoglobin and hemoglobin are both what?
Oxygen binding molecules
How much of the erythrocytes (by weight) does Hemoglobin make up?
Describe the structure of myoglobin
myoglobin consists of a single polypeptide (globin) chain with 1 heme prosthetic group
Describe the structure of hemoglobin
Hemoglobin is a globular protein with quaternary structure
4 globin chains (tetramer) - 2 alpha, 2 beta
the 2 alpha monomers plus the 2 beta monomers make 2 alpha beta dimers resulting in a tetramer held together by hydrophobic interactions
Hemoglobin's alpha and beta globin chains are each similar to...
myoglobin! but only have 18% identical amino acids
each globin chain binds 1 heme prosthetic group
The distal His is at the top
it maintains the iron II state when the O2 isn't bound
Stabilizes oxygen's hydrogen bonding
The proximal His is at the bottom
coordinately bound to iron
What happens when Hb binds O2?
The heme Fe moves into the plane of the porphyrin ring
Describe the binding curves of Hb and Mb
What does a sigmoidal curve mean?
Differences in Mb and Hb saturation
- -readily saturates in lung
- -releases 66% of bound O2 in tissues
- Mb-remains near saturation (91%) in tissues
- -not a transporter
How does oxygen binding affect the Hb tertiary structure?
- ligand binding affects iron position in the porphyrin ring
- movemeny of iron affects proximal His (interacts with Fe)
- affects helix position and tertiary structure
Describe the 2 major conformations of Hb
Deoxyhemoglobin --> T State
- iron out of plane of porphyrin ring
Oxyhemoglobin --> R State
- relaxed state
- iron in plane
oxygen binding leads to changes in the Hb quaternary structure. How so?
- Changes at the heme group cause changes in the tertiary structure
- leads to changes in the quat structure
What are the two models to explain the T to R transition? Explain them.
- -entire protein is either in the T or the R state
- -ligand binding shifts the entire tetramer simultaneously from T to R
- Sequential-Binding of ligand to one subunit changes conformation of that subunit from T to R
- -each monomer is in the T or R state
**ligand binding in hemoglobin is most likely a combo of the two models
Other models of cooperativity (name 4)
- Symmetry Rule
Describe Hill plots
- Hill plots are used to describe cooperativity.
- In a hill plot, nh is the hill coefficient, found by the slope of the line.
- if nh < 1 there is negative cooperativity (this would mean binding one prevents binding of next - not really observed)
- if nh=1 there is no coop
- if nh >1 positive coop (binding 1 facilitates binding of next)
Why is cooperativity in Hb important?
- it allows for the binding and release of oxygen at physiological conditions
- (it is determined and affected by residues in the alpha and beta monomers)
What regulates Hb oxygen binding and release?
- 2,3-BPG- stabilizes the T state (through H-bonds and electrostatic interactions)
- - faciliatates release
- - allosteric effector
*note: 2,3 BPG keeps the t-state for a while and lowers oxygen affinity but eventually oxygen will bind again lower affinity doesn't mean never bind
small molecules that bind a protein and change conformation, altering protein function
inhibits or activates binding of ligand
What happens to the saturation curve with more or less BPG?
- therefore less BPG = quicker saturation, larger keq
Hemoglobin is constrained by?
interactions between alpha and beta monomers
What stabilizes the T state?
Networks of ion pairs and H bonds. Breaking any of these interactions destabilizes the T state and increases ligand affinity.
How does the affinity of Hb for oxygen change as pH decreases?
- As pH decreases, protons are added to the key His residues that stabilize the T state.
- -stablizes interactions between monomers
- -decreases oxygen affinity
About 80-85% of CO2 that diffuses into the blood is converted to ...
bicarbonate and H+ within RBCs
What is the regulation of Hb ocygen binding by H+ ions and CO2 called?
The Bohr effect
The remaining ____ of CO2 in blood reacts with N termini of alpha globin chains through a non - enzymatic reaction called ____.
- -carbamylation further stabilizes the T state
- -decreases O2 saturation of Hb beyond that caused by a drop in blood pH
What affects Hb/O2 binding and release?
- proton concentration
- CO2 concentration
- allosteric effectors
- mutations -->hemoglobinopathies
Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin
- the beta adult subunit is replaced by a gamma subunit
- -about 72% identity
- -reduced affinity for 2,3 - BPG
allows for O2
to be transferred from mother to fetus
Sickle Cell anemia
- results from inheriting 2 alleles for a hemoglobin variant HbS
- HbS molecules aggregate forming fibrils that cause RBS to form sickle shape
- In HbS, Glue 6 on beta chains is replaced with a Val that can interact with hydrophobic areas on other beta subunits
- the most severe sickle cell symptoms occur in low oxygen environments
- the hydrophobic areas are only exposed in the T state - anything that stabilizes the T state will increase the amount of fibrillar HbS
What would you like to do?
Home > Flashcards > Print Preview