Day 5 - Oxygen Transport

How do heme proteins participate in protecting cells? (3)

- sequestering O2

- limiting the production of ROS

- detoxifying them

What are the 2 major heme proteins?

- myoglobin (Mb)

- hemoglobin (Hb)

What is the principal function of O2?

to serve as an electron acceptor in oxidative metabolism

What is the O2-binding moiety common to Hb and Mb?

heme

What makes up the outer portion of a heme molecule?

4 pyrrole rings

What is at the center of heme?

Fe2+. iron (ferrous ion)

What 2 things are involved in the initial steps of heme synthesis?

succinyl-CoA and glycine

Human Hb is a tetramer consisting of ______ and ______.

- 2 alpha globin polypeptides

- 2 beta globin polypeptides

Where is myoglobin found? (3)

- cytosol of skeletal

- cardiac cells

- smooth muscle cells

True or False: Mb a tetramer protein.

False! it is a monomeric protein.

When the Hb subunits are examined together, the 4 molecules function as _________.

heterodimers

How do the oxygen saturation curves for myoglobin and hemoglobin differ?

- hemoglobin = sigmoidal

- myoglobin = typical rapid oxygen concentration-dependent saturation of a monomeric protein

The oxygen of Hb is modified by several factors:

1. Binding of O2 to Hb [increases/decreases] O2 affinity.

2. Binding of CO2 to other specific sites [increases/decreases] O2 affinity.

3. Binding of protons to specific basic groups [increases/decreases] O2 affinity.

4. Binding of certain organic phosphates [increases/decreases] O2 affinity.

1. increases

2. decreases

3. decreases

4. decreases

What are the 4 types of Hb?

- oxyhemoglobin

- deoxyhemoglobin

- carbaminohemoglobin

- carboxyhemoglobin

What are the relaxed and tense states for Hb?

- relaxed = oxyhemoglobin

- tense = deoxyhemoglobin

Are interactions between heterodimers stronger or weaker in the relaxed state?

stronger

What has higher affinity for O2, R state or T state?

R state

What are the implications of a left-shifted oxygen-Hb desaturation curve?

- increased O2 affinity (r state)

- reduced oxygen delivery to tissues

What is a left-shifted oxygen-Hb desaturation curve caused by?

- high pH

- low temp

- low 2,3-BPG

- fetal Hb

- methemoglobinemia

- high O2 affinity Hb variants

What are the implications of a right-shifted oxygen-Hb desaturation curve?

- reduced O2 affinity ( T state)

- increased oxygen delivery to tissues

What is a right-shifted oxygen-Hb desaturation curve caused by?

- low pH

- increased CO2

- high temp

- high 2,3-BPG

- low O2 affinity Hb variants

What 2 things positively affect the O2 binding affinity of Hb?

- O2

- H+

What 2 things negatively affect the O2 binding affinity of Hb?

- CO2

- 2,3-BPG

What is the Bohr Effect? (for sure on test)

O2 binding to Hb is very sensitive to pH

How does the O2 saturation curve shift with a decrease in pH (Bohr Effect)?

shifts right

How does CO2 affect Hb?

shifts the equilibrium to the T state and promotes release of O2

How does temp affect Hb?

with increased temp, O2 affinity for Hb decreases