Hemoglobin Production

Hemoglobin is made up of ______ and ______.

heme (protoporphyrin IX + Fe), globin (protein)

Hemoglobin accounts for ______ of the RBC cytoplasm.

95%

Heme is composed of a ______ with an atom of ______ in the middle.

protoporphyrin IX, Fe+2

Heme can combine _______ with 1 O2.

reversibly

Heme is what gives blood its ______.

red color

Globin is made up of two pairs of two ______.

polypeptide chains

The polypeptide chains are both ______ and ______ in shape.

helical, non-helical

The complete hemoglobin molecule is made up of ______ and ______.

4 heme, 4 globin

Hemoglobin has the capacity to carry ______ O2 molecules.

4

Heme synthesis occurs in the ______, in the mitochondria and cytoplasm of _______ precursors.

bone marrow, erythrocyte

Globin synthesis is general _______.

protein synthesis (from mRNA)

Synthesis of protoporphyrin begins in the ______.

mitochondria

Here, ______ is formed from glycine and succinyl-CoA.

delta-aminolevulinic acid (d-ALA)

The enzyme ______ is needed for d-ALA formation.

aminolevulinate (d-ALA) synthetase

The formation of d-ALA is the most highly ______ step of protoporphyrin formation.

regulated

Porphyrinogens are the unstable inactive form of ______.

porphyrin

_______ is an inherited defect in heme synthesis.

Porphyrias

Step 1 of heme synthesis

Succinyl-CoA + glycine + d-ALA synthase = d-ALA

This step occurs in the _______.

mitochondria

Step 2 of heme synthesis

Formation of porphrynogens

Where does this occur?

Cytosol

Step 3 of heme synthesis

Protoporphyrin IX + ferrochelatase = heme

Where does this step occur?

Nucleus

Ferric iron

Fe3+

Ferrous iron

Fe2+

Ferric 3+ iron is transported to the RBC membrane by ______.

transferrin

Once inside the RBC, ferric 3+ iron gets reduced to ferrous 2+ iron in the ______.

mitochondria

Only ______ iron can be incorporated into heme.

ferrous 2+

It is incorporated into heme with ______.

ferrochelatase

Excess iron aggregates into ______ (storage form on iron).

ferritin

Hemoglobin A polypeptide chains

2a, 2B

Hemoglobin A2 polypeptide chains

2a, 2delta

Hemoglobin F (intrauterine/fetal) polypeptide chains

2a, 2y

Before birth, what hemoglobin is present?

Hb F

At birth, what hemoglobins are present?

Hb F (a + y) 60-90%

Hb A (a + B) 10-40%

During adulthood, what hemoglobins are present?

Hb F (a + y) 1-2%

Hb A (a + B) 95%

Hb A2 (a + delta) 3.5%

ALA synthase is inhibited by ______.

heme

Globin transcription is regulated by ...

promoter, Kruppel-like factor 1, TFs, locus control region

Globin translation is inhibited in the absence of, and increased in the presence of ______.

heme

Hemoglobin is stimulated by tissue ______.

hypoxia

This causes increased ______ release.

EPO

The function of hemoglobin is to bind ______ at the lungs and unload it in the tissues.

oxygen

Hemoglobin has a ______ affinity for O2 in the lungs.

high

Hemoglobin has a ______ affinity for O2 in the tissues.

low

O2 affinity is dependent on ______.

pO2

An oxygen-dissociation curve plots ______ vs ______ of Hgb.

pO2, %O2

A left shift of this curve is caused by ______ H+, BPG, pCO2, temperature.

decreased

When the curve shifts left, there is an ______ in O2 saturation and o2 affinity.

increase

A right shift of this curve is caused by ______ H+, BPG, pCO2, temperature.

increased

When the curve shifts right, there is ______ O2 saturation and O2 affinity.

decreased

Deoxyhemoglobin T structure is ______.

spherical (with a central cavity)

Oxyhemoglobin R configuration facilitates additional binding of ______.

oxygen

What is present in deoxyhemoglobin, but absent in oxyhemoglobin?

DPG/BPG (2,3-di/bisphophoglycerate)

Methemoglobin contains ______ iron.

ferric 3+

Why is this an issue?

Fe3+ cannot bind to O2, causing cyanosis

How can methemoglobin be detected?

Spec. - 630nm

Brown blood

How can methemoglobin be corrected?

- O2 inhalation

- Reducing substances

Sulfhemoglobin occurs when hemoglobin is oxidized by certain ______.

drugs/chemicals (ex. sulfonamides)

Why is this a problem?

O2 affinity is increased, leading to cyanosis

How is sulfhemoglobin detected?

Spec. - 630nm

How can sulfhemoglobin be corrected?

It can't - irreversible

Carboxyhemoglobin occurs when ______ binds to heme iron.

CO

Why is this a problem?

CO has much larger affinity for O2, leading to bad cyanosis and necrosis

How can carboxyhemoglobin be detected?

Spec. - 540nm

Cherry red blood

How can carboxyhemoglobin be corrected?

Remove CO, provide 100% O2

With CO2 in the blood, the curve will shift ______.

right

Without CO2 in the blood, the curve will shift ______.

left

Upon hemolysis, ______ becomes saturated with hemoglobin.

haptoglobin

The complex is then ______ safely.

degraded

Hemoglobin has the highest affinity for O2 when the pO2 is ______.

high

Fe binds to ______ in hemoglobin.

O2

The majority of Fe is stored in ______.

mature RBCs

DMT1 transports Fe across the ______ of enterocytes.

luminal side

______ binds to Fe to transport it through plasma.

Transferrin

Total iron-binding capacity measures Fe ______.

transport