Red Blood Cell Physiology

Question 1

How do RBC uptake glucose

Answer 1

• glut 1 transporter

Question 2

Describe confirmations of glut transporter and how it takes in glucose

Answer 2

• has 2 conformations
  1 T1 with glucose binding site exposed to outer surface
  2 T2 with glucose binding site exposed to inner surface
• brings in glucose through changing between conformations

Question 3

Describe glut 1 transporter structure as functions in RBC’s

Answer 3

• low level uptake of glucose required to sustain respiration in all cells
• Vit C uptake as part of compensation in non vit C producing mammals
• in RBC is a type 3 integral protein with 12 hydrophobic segments each forming a membrane spanning transmembrane channel
• side by side assembly of several helixes produce a transmembrane channel lined with hydrophilic residues that can H2 bond with glucose as it moves through

Question 4

Describe protein synthesis by reticulocytes in and out of circulation

Answer 4

• have numerous organelles and r active in protein synthesis
• in circulation lose organelles in about 24 hours and become young RBC and gradually lose ability to synthesize proteins

Question 5

Properties of glut 1 in RBC
Concentration
Rate of uptake

Answer 5

• 2% of protein on RBC membrane
• exhibit specificity for glucose and D hexoses ( L hexoses not uptake )
• functions at 75% Vmax at physiological glucose blood conc and can be inhibited by analogs
• not insulin dependent
• 492 aas sequence has been determined
• 12 transmembrane helical segments
• generates gated pore in membrane

Question 6

Describe superoxide reactions
Reactions
How formed in RBC and other tissues
How dealt with

Answer 6

• O2 + e + O2-
• formed in RBC by auto oxidation of HB to metheHB ( 3% of all Hb per day )
• in other tissue through xathine oxidase or cytochrome P450 reductase
• spontaneously dismutases into H2O2 + O2 and reaction sped up by superoxide dismutase O2-+ O2- + 2H+ = H202 + O2

Question 7

What does catalase do

Answer 7

• H2O2 = 2H2O + O2

Question 8

Difference between pro oxidants and antioxidants

Answer 8

• reactions and components that generate potentially toxic oxygen species
• reactions and components that dispose, scavenge, suppress formation or oppose actions of reactive oxygen species
  ( NADPH , GSH , Vit E , Catalase , Superoxide dismutase )

Question 9

What can shift balance of pro and antioxidants towards pro oxidants.

What is this state called and it’s effects

Answer 9

• increased production of ROS following ingestion of drugs and chemicals
• antioxidants diminished due to inactivation of enzymes or conditions that cause low levels of the components
• oxidative stress leading to cell injury and death if stress massive or prolonged

Question 10

List causes of oxidative stress and 4 effects

Answer 10

• alcohol , pesticides, poor diet , excessive exercise , inadequate physical activity , medication or treatment, air and water pollutants , exposure to toxins
• ionizing radiation, anaerobic metabolism, radical generators
• nucleic acid damage
• lipid peroxidation
• protein oxidation
• cell injury and death

Question 11

Describe glutathione reactions and NADPH ( the one to revive GSH )

Answer 11

• 2GSH + ROOH = GSSG + H2O + ROH
• OH neutralized
• GSSG + NADPH + H = 2GSH + NADP+
  Enzyme is glutathione reductase

Question 12

List at least 2 diseases for the following organs due to oxidative damage 
Brain 
Lung 
Joints 
Kidney 
Skin 
Heart
Eyes
Immune system 
Multi organ 
Blood vessels

Answer 12

• cancer , stroke , migraine , Alzheimer’s
• COPD , cancer, asthma
• rheumatoid, osteoarthritis
• chronic kidney disease , nephritis
• melanoma , skin aging, dermatitis
• isaemia, myocardial infarction , hypertension
• cataracts , retinal degeneration
• autoimmune , cancers
• aging, chronic fatigue , diabetes
• atherosclerosis, hypertension, endothelial dysfunction

Question 13

What maintains RBC lemma integrity

Answer 13

• since they can’t synthesize proteins integrity maintained with replenishment of anti oxidants

Question 14

List the 3 major metabolism pathways in RBC and what they do

Answer 14

1 glycolysis by Embden Meyerhof pathway - 70% ATP for lemma ion pumps and NADP for metheHB reduction

2 pentose phosphate pathway - supplies NADPH to maintain reduced state of glutathione

3 2,3 BPG to control affinity for O2 in Hb

Question 15

What is the major ATP generation pathway in RBC

And why

Answer 15

• no mito so no krebbs so it’s glycolysis ( 95% )

Question 16

Effect of Pentose pathway in RBC’s

Effect of low GSH

Answer 16

• makes NADPH to reduce Glutathione and inhibit G6PDH by feedback inhibition
• Ribose 5 made
• GA3P and F6P for glycolysis made
• increased peroxide’s that weaken cell and cause hemolysis and increased oxidation of Hb to metheHB wc also weakens cells

Question 17

Summarize the hexose monophosphate pathway

Describe 2,3 BPG shunt

Answer 17

• entire phosphate pentose pathway and glucolysis up to GA3P
• 1,3 BPG can be converted into 2,3 BPG which itself can made into 3 phosphoglycerate

Question 18

Effects of deficiency of G6PDH
Why are RBC so sensitive to oxidative damage

3 scenarios that can lead to hemolytic anemia

Answer 18

• PPP is only pathway to make NADPH in RBC so they are very sensitive to oxidative damage if pathway damaged
• most common enzymopathy leading to hemolytic anemia
• broad beans ( Vicia Faba ) In deficient individuals can precipitate an attack due to having potential oxidants
• drugs eg antimalarial primaquine lead to attack and is called primaquinesensitive
• sulfonamides ( napthalene ) precipitate an attack cause they lead to H2O2 and O2 generation