BIOCH200 Lecture Notes - Lecture 10: Bohr Effect, Hemoglobin

79 views2 pages

turquoisewalrus441

1 May 2018

School

University of Alberta

Department

Biochemistry

Course

BIOCH200

Professor

Jonathan Parrish

For unlimited access to Class Notes, a Class+ subscription is required.

Allosteric Effectors of Hemoglobin

1. Oxygen → favours R state (Positive effector)

2. BPG → favours T state (negative effector/heteroallostery)

3. H+ → Favours T state (negative effector heteroallostery)

4. CO2 → favours T state (negative effector heteroallostery)

2,3-Bisphosphoglycerate (BPG)

❏Essential in stabilization of T state

❏Small and highly negative

❏Inhibits oxygen binding

❏Binds to central cavity of deoxyhemoglobin (T-state) → Negative charge interacts with the

positive charged groups of the protein (4His, 2 Lys and 2N-terminus residues)

❏Can not bind to central cavity of oxyhemoglobin (R-State)

H+ Ions

❏Facilitate formation of T-state → Enhance BPG binding

❏[CO2] is kept low to produce more carbon dioxide.

❏Effect of [H+] (pH) on hemoglobin oxygen is called bohr effect.

❏More active = more CO2 = more HCO3- and H+ = decreases pH

Hydrogen Ions and Hb

❏Metabolism generates protons = lowers pH. (ADP and HCO3 production).

❏Lower pH leads to protonation of side chains (His and N-terminus)

❏Groups associated with BPG become protonated (enhance BPG, decrease oxygen binding)

❏Subunit interface is affected (ion pairs formed) → new electrostatic interactions form → Bohr

Effect.

❏Therefore, presence of carbon dioxide means the release of oxygen because there is more

electrons.

The Bohr effect and physiological significance

❏Homoallosteric, quaternary, cooperative.

❏High [H+] means decreased oxygen binding (negative inhibitor) → further from y-axis →

protonated means BPG binds = T-State

Combined Effects of Oxygen, BPG, CO2 and pH on Hb function

❏Presence of equilibrium dependent on presence of carbon dioxide, BPG, and [H+], and on the

ppO2. [O2] = major determinant.

❏Proportion of molecules in T or R state determines how much oxygen is bound or released.

❏Lungs have high ppO2 and a relatively high pH → R state favored. When oxygen binds it triggers

switch to R form → Pulls up F helix for Oxygen binding.

❏Actively respiring tissues have low pH = Lots of CO2 and a low ppO2 → T-State favoured →

oxygen released. → Lots of ATP used.

Functions of Proteins

❏Determined by their structure

❏Amino acid substitutions can cause huge errors or physiological significance.

❏Sickle Cell → genetic disease → Critical substitution

❏Fetal Hemoglobin → Physiological adaptation

Fetal Hemoglobin

❏2 alpha and 2 gamma (no beta)

❏Gamma is homologous to adult beta subunit → substitution of His143 for a Ser.

❏His involved in BPG binding (2 His in central cavity)

Unlock document

This preview shows half of the first page of the document.
Unlock all 2 pages and 3 million more documents.

Already have an account? Log in

Document Summary

Allosteric effectors of hemoglobin: oxygen favours r state (positive effector, bpg favours t state (negative effector/heteroallostery, h+ favours t state (negative effector heteroallostery, co2 favours t state (negative effector heteroallostery) Binds to central cavity of deoxyhemoglobin (t-state) negative charge interacts with the positive charged groups of the protein (4his, 2 lys and 2n-terminus residues) Can not bind to central cavity of oxyhemoglobin (r-state) Facilitate formation of t-state enhance bpg binding. [co2] is kept low to produce more carbon dioxide. Effect of [h+] (ph) on hemoglobin oxygen is called bohr effect. More active = more co2 = more hco3- and h+ = decreases ph. Metabolism generates protons = lowers ph. (adp and hco3 production). Lower ph leads to protonation of side chains (his and n-terminus) Groups associated with bpg become protonated (enhance bpg, decrease oxygen binding) Subunit interface is affected (ion pairs formed) new electrostatic interactions form bohr.

Related Questions

1. The dominant motif found in hemoglobin and myoglobin is: a) twisted beta sheet b) beta barrel c) helix-loop-helix d) 7-TM 2. Myoglobin has how many polypeptide chains? A) 1 b) 2 c) 3 d) 4 3. Structurally and functionally, hemoglobin closely resembles a(n) a) transmembrane protein b) mucopolysaccharide c) bile salt d) allosteric enzyme 4. The oxygen binding site in hemoglobin and myoglobin is called: a) BPG b) heme c) proximal-His d) N-terminal carbamate 5. The proximal His residue in hemoglobin and myoglobin binds to which atom or molecule? A) CO2 b) O2 c) Fe d) BPG 6. The distal His residue in hemoglobin and myoglobin binds to which atom or molecule? A) CO2 b) O2 c) Fe d) BPG 7. BPG binds to: a) N-terminal carbamate b) proximal His c) heme group d) central cavity 8. Indirect activity of CO2 is a result of increased concentration of which chemical species? A) BPG b) H+ c) heme iron d) distal His 9. Direct activity of CO2 is a result of binding to which molecular feature? A) the heme group b) the N-terminal ends of the 4 polypeptide chains c) the central cavity d) the proximal His 10. The sigmoidal, cooperative binding curve commonly observed for hemoglobin is a result of: a) competition between CO2 and O2 for heme binding. B) competition between heme and distal His for O2 binding c) competition between BPG and CO2 for binding at the central cavity site d) T to R transition 11. Hemoglobin has a tendency to release its oxygen to the tissues because: a) in this region pH is high and O2 concentrations are low b) in this region both pH and O2 concentrations are low c) in this region both pH and O2 concentrations are high d) there is much BPG in this region 12. Which statement about fetal hemoglobin is not true? A) fetal hemoglobin has gamma chains instead of beta chains b) fetal hemoglobin binds BPG less strongly than maternal hemoglobin c) fetal hemoglobin binds oxygen less strongly than maternal hemoglobin d) fetal hemoglobin binds oxygen more strongly than maternal hemoglobin 13. Which process is most responsible for the sickling of cells seen in sickle cell disease? A) aggregation of the oxygenated R form of hemoglobin-S to form insoluble fibers b) aggregation of the deoxygenated T form of hemoglobin-S to form insoluble fibers c) Hemoglobin-S does not contain heme d) Hemoglobin-S contains a mutant form of heme which will not bind oxygen 14. A person with sickle-cell trait is very unlikely to catch which disease? A) malaria b) colon cancer c) avian flu d) whooping cough 15. A person with a genetic defect which results in the synthesis of an insufficient amount of the alpha chain of hemoglobin is said to have which disease? A) alpha thalassemia b) beta thalassemia c) pernicious anemia d) Crohnâs disease

Match the words (A-E) with the statements below: ( 10 pts)

A. Bohr

B. 2, 3-BPG

C. Carbamate

D. Carbon dioxide

E. Concerted

F. Distal Histidine

G. Heme

H. Hemoglobin

I. Myoglobin

J. Sickle Cell Anemia

This has the ability to protect against carbon monoxide binding to the heme _______________

This is the molecule whose function is to facilitate diffusion of oxygen in muscle cells. ___________

The ability of myoglobin to bind oxygen depends on the presence of a bound prosthetic group called .

The shape of this protein has a sigmoidal curve _______________

As the partial pressure of ___________ increases, the affinity of oxygen binding to hemoglobin decreases. (there can be two answers)

The effect of hydrogen ions and carbon dioxide on the binding of oxygen to hemoglobin is called the _____________ effect

___________ is an allosteric effector that binds to the positive charges on the hemoglobin molecule .

Hemoglobin binding of oxygen is best described as a combination of sequential and ______________ model.

Carbon dioxide forms ______________ groups in proteins by reaction with N-terminal groups.

This condition is a result of a single-point mutation in the Î² chain of hemoglobin:__________________

BIOCH200 Lecture Notes - Lecture 10: Bohr Effect, Hemoglobin

Document Summary

Get access

Related Documents

BIOCH200 Lecture Notes - Lecture 14: Alpha Helix, Myoglobin, Coordinate Covalent Bond

BIOCH200 Lecture Notes - Myoglobin, Hemoglobin, Hydrolysis

BIOCH200 Lecture Notes - Fetal Hemoglobin, Tetrameric Protein, Hemoglobin A

Related Questions