Hemoglobin Pathways

Hemoglobin is comprised of how many monomers? What two components comprise a monomer? How many dimers?

1. Four monomers

2. Globin chain and heme

3. Two dimers

What is a tetramer?

2 equivalent dimers

How is Protoporphyrin IX different from a regular hemoglobin molecule?

It’s a tetra-porphyrin ring with one Ferrous Iron

How many molecules of oxygen does one Fe2+ carry?

One

Can an O2 molecule attach to Fe3+?

No

Where are globins produced? What produces them?

1. Cytosol

2. Polyribosomes

What are the two kinds of adult globins?

1. Beta

2. Delta

What are the two kinds of fetal globins? Which one is the primary fetal globin?

1. Gamma (primary)

2. Alpha

What are the two kinds of embryonic globins?

1. Epsilon

2. Zeta

HGB A is comprised of what two globin chains?

2 alpha, 2 beta

HGB A2 is comprised of what two chains?

2 alpha, 2 delta

HGB F is comprised of what two chains?

2 alpha, 2 gamma

HGB Gower is a category that comprises how many different hemoglobin molecules?

Three

What chains comprise two out of the three Gower HGB molecules?

1. 2 alpha, 2 epsilon

2. 2 zeta, 2 epsilon

What is the third type of Gower HGB molecule called, and what chains comprise it?

1. HGB Portland

2. 2 zeta, 2 gamma

What chains comprise HGB H? Why?

1. 4 beta

2. Insufficient alpha chains

What chains comprise HGB S? Why?

1. 2 alpha, 2 beta

2. Beta chains are defective

What kind of chains is HGB Barts comprised of? Why? Is HGB Barts conducive to life?

1. 4 gamma

2. Insufficient alpha

3. No - babies will not survive

What color is Oxyhemoglobin and what is this form called?

1. Bright Red

2. Relaxed (“R”)

What color is deoxyhemoglobin and what is it called?

1. Dark red

2. Tense (“T”)

What is responsible for hemoglobin’s ability to pick up and release O2 molecules?

Its quaternary structure

What does it mean to call hemoglobin an “allosteric” Protein?

It means hemoglobin is altered by other molecules

What is one allosteric regulator of HGB and what does it do to HGB? How can it do this?

1. 2,3-DPG

2. Binds to the central cavity of deoxyhemoglobin

3. It’s attracted to positive charges of beta chains

What keeps HGB in deoxy state until it reaches the lungs?

Salt bridges formed by 2,3-DPG

2,3-DPG is a product of which pathway?

Rapoport-Luebering Shunt

What does it mean when oxygen has “cooperative binding”?

It means O2 binds more readily to HG that already has some binding sites occupied

When does oxygen have the greatest affinity for HGB?

When HGB has 3 out of 4 binding sites occupied

What does a lift shift mean?

1. Increased O2 affinity

2. Decreased O2 unloading

What does a right shift mean?

1. Decreased O2 affinity

2. Increased O2 unloading

What causes a left shift?

1. Decreased pCO2

2. Increased pH (alkalosis)

3. Decreased 2,3-DPG

4. Decreased Temp

5. Abn Hemoglobins

6. Increased CO

What causes a right shift?

1. Increased pCO2

2. Decreased pH (acidosis)

3. Increased 2,3-DPG

4. Increased temp (fever)

What are two means of CO2 removal?

1. Bicarbonate in plasma

2. Some in RBC’s

What is the Bohr Effect?

When deoxyhemoglobin takes up H+, oxyhemoglobin releases H+, and HGB acts as a buffer

What is Methemoglobin? In what percentage of overall HGB is it normally found?

1. Iron is in Ferric state (Fe3+) and can’t bind or transport O2

2. 1.5-2% per day

What are three causes of increased Methemoglobin?

1. Environmental exposures (nitrites)

2. Inherited pathway defects

3. Inheritance of HGB M

Can ferric iron be reversed?

Yes

What color does HGB M produce in blood?

Chocolate brown

What is Sulfhemoglobin, and is it reversable?

1. Sulfur attached to HGB

2. No

What is the normal concentration of SHb?

0.5-2.2%

What causes abnormal amounts of SHb?

Exposure to sulfur-containing drugsor environmental factors, such as certain foods or chemicals.

What is Carboxyhemoglobin?

CO attached to heme

How much higher of an affinity does CoHb have for CO compared to O2?

200X higher affinity

Is CO reversible?

Yes

What is the normal concentration of CoHb?

< 7%

High concentrations of CoHb are caused by what three things?

1. Smoking

2. Polluted environment

   1. Exposure to high levels of CO

What color does CoHb turn skin?

Cherry red