Structure and Function of Erythocytes

What are Erythrocytes?

Red blood cells

What are the three cellular components of the blood?

1. Red Blood Cells

2. White Blood Cells

3. Platelets

What contains the red pigment in red blood cells?

when the iron in hemoglobin binds to oxygen

Do Red blood cells have organelles?

No

What shape does the RBC have?

Biconcave disc shape

What do the RBCs help maintain the proper amount of?

oxygen

What type of blood are is carried by the veins?

deoxygenated

What type of blood is carried by the arteries?

Oxygenated

What do the RBC transport from the lungs to the tisues?

Oxygen

What do the RBC transport from the tissues to the lungs?

Carbon dioxide (waste product)

What is the role of plama membrane proteins?

Help with maintaining the biconcave shape of RBCs

What is it called when the proteins come together to form a lattice-like network?

The cytoskeleton

What is the cytoskeleton anchored to?

the inner surface of the RBC plasma membrane

What are the two most abundant proteins in the cytoskeleton lattice?

• Spectrin

• actin

What does spectrin create chains of?

heterodimers

What do the chains of heterdimers consist of?

ɑ- and β-spectrin

Where do the spectrin dimers join at?

junctional complex

What is the junctional complex made of?

• actin

• band 4.1

• actin-binding proteins

How is the junctional complex tethered to the cell membrane?

By glycophorin (membrane protein)

What helps to anchor the cytoskeleton lattice to the cell membrane?

• Ankyrin

• band 3

• band 4.1

• band 4.2

What role does the cytoskeleton lattice in the RBC?

provides stability and flexability

What is Sickle Cell Disease?

alters the shape and function of the hemoglobin (Hb) molecule in red blood cells to take on the shape of a sickle (or crescent)

In what population is Sickle Cell disease (SCD) most prevalent?

African, South or Central American, Caribbean, Mediterranean, Indian, or Saudi Arabian descent.

What are the four primary Sickle Cell Disease (SCD) genotypes?

1. HbSS

2. HbSβ0-thalassemia

3. HbSC

4. HBSβ+- thalassemia

What are the two most clinically severe forms of Sickle Cell?

HbSS and HbSβ0-thalassemia

What are HbSS and HbSβ0-thalassemia collectively known as?

Sickle Cell anemia (SCA)

What are the two more clinically benign forms of Sickle Cell Disease?

HbSC and HbSβ+

What single point mutation causes Sickle Cell?

Glutamate → Valine

What does the hemoglobin structure consist of?

four heme groups and four globin chains

What is the heme part of hemoglobin?

Fe(II)-protoporphyrin IX

What is the active form of Iron?

Fe+2 = ferrous

The Porphyrin ring provides _ of the 6 ligants surrounding the iron atom.

four

What two steps of Heme synthesis occur in the mitochondrai?

First and last steps only

Where do the rest/ middle steps of heme synthesis take place?

In the cytosol

What are the starting substances for heme synthesis?

Glycine + Succinyl CoA

What enzyme converts Glycine + Succinyl CoA → δ-Aminolevulinic acid?

ALA Synthetase (δ-Aminolevulinic acid Synthetase)

What is ALA?

δ-Aminolevulinic acid

What is step 1 of heme synthesis?

Glycine + Succinyl CoA → δ-Aminolevulinic acid

What is step 2 of heme synthesis?

δ-Aminolevulinic acid → Porphobilinogen

What enzyme is used to convert δ-Aminolevulinic acid → Porphobilinogen?

ALA dehydratase

What enzyme is inhibited by Pb?

ALA dehydratase and Ferrochelatase

What is step 3 of heme synthesis?

Porphobilinogen → Hydroxymethylbilane

What enzyme is used to convert Porphobilinogen → Hydroxymethylbilane?

Porphobilinogen deaminase

What is another name for the enzyme Porphobilinogen deaminase?

Hydroxymethylbilane synthase

What is the 1st Porphyrin of the heme synthesis pathway?

Hydroxymethylbilane

What is step 4 of heme synthesis?

Hydroxymethylbilane → Uroporphyrinogen-III

What enzyme is used to convert Hydroxymethylbilane → Uroporphyrinogen-III?

Uroporphyrinogen III synthetase

What is step 5 of heme synthesis?

Uroporphyrinogen-III → Coproporphyrinogen-III

What enzyme is used to convert Uroporphyrinogen-III → Coproporphyrinogen-III?

Uroporphyrinogen decarboxylase

What is the last step of heme synthesis?

Protoporphyrin-IX → Heme

What enzyme is used to convert Protoporphyrin-IX → heme?

Ferrochelatase

What is added to the last step of heme synthesis?

Fe+2 ion

What does the suffix -in mean?

colored

What does the suffix -ogen mean?

colorless

What cofactor does ALA synthetase require?

B6 = PLP

What is vitamin B12?

Cobalamin

Vitamin C is used to convert Fe+_ to Fe+_

Fe+3 → Fe+2

What is the Fe-sensing complex controlled by?

hepcidin

What is the Fe-sensing complex made up of?

HFR, ß2-macroglobulin + other proteins (complex)

What is Transferrin receptor?

an iron carrier

What is TIBC?

Total Iron-Binding Capacity

WHat does the Blood iron test look at?

TIBC (Total Iron-Binding Capacity)

How saturated should Transferrin be?

1/3 saturated

What does high TIBC indicate?

Iron deficiency

What does low TIBC indicate?

Iron overload

What does High TIBC mean in terms of openings?

Lots of openings for iron to bind to

What does Low TIBC mean in terms of openings?

very little openings for iron to bind to

What is the treatment for hemochromatosis?

• chelation therapy

• Plebotomy

• Deferoxamine (binds Fe, urine)

How many places does Billirubin metabolism occur in?

four places

• Spleen

• Blood

• Liver

• Intestine

Where does Heme convert to Billirubin?

Spleen

Where is Bilirubin-albumin synthesized?

In the blood

Where is Bilirubin diglucuronide synthesized?

In the liver

Where are Urobillinogen Bile pigments transfered to the feces?

In the intestines

How many types of Heme oxygenase are there?

3 types

• I

• II

• III

What is the only place CO is produced?

Bilirubin Metabolism Step 1 (Heme → Biliverdin)

What does hemolysis of older RBC release?

hemoglobin

What is heme metabolized in?

Histiocytes

Production of biliverdin releases what?

Carbon Monoxide (CO)

What effect does Hemolysis have on bilirubin?

Increases indirect bilirubin

What effect does the Crigler-Najjar syndrome have on billirubin?

Increases indirect bilirubin

What effect does the Gilbert syndrome have on bilirubin?

Increases indirect bilirubin

What effect do low levels of conjugation enzymes in newborns have on bilirubin?

Increases indirect bilirubin

What effect does hepatic damage in the liver have on bilirubin?

Increases indirect bilirubin

What enzyme converts Bilirubin → Bilirubin diglucoronide?

UDP-glucuronyl transferase (UGT)

WHat effect does hepatic damage in the intestine have on bilirubin?

increases direct bilirubin

What effect does Bile duct obstruction (clay-colored stools) have on bilirubin?

increases direct bilirubin

What effect does Dubin-Johnson (black pigmentation in liver) have on bilirubin?

increases direct bilirubin

What effect does Rotor syndrome have on bilirubin?

increases direct bilirubin

How is UGT activated?

In the presence of light

When is UGT generally inactive?

in newborns