L7-metabolic Pathways In RBCs

Question 1

What is the importance of other metabolic pathways in RBCs

Answer 1

For keeping the integrity of the RBC’s membrane or forgetting rid of the Bilirubin released during hb breakdown

Question 2

What are the other pathways

Answer 2

Hexose monophosphate shunt and uronic acid pathway which both occur in the cytoplasm

Question 3

What is the importance of the Hexose monophosphate chant

Answer 3

Parallel pathway to glycolysis that takes glucose 6 phosphate produced by glycolysis and converts it to fructose 6 phosphate and glyceraldhyde 3 phosphate while generating NADPH in the process

Question 4

What are the steps of hexose monophosphate shunt

Answer 4

First step is the conversion of glucose 6 phosphate to ribose 5 phosphate which generates two NADPH
it includes an irreversible oxidative phase followed by a series of reversible sugar phosphate interconversions

Question 5

How is the Hexose monophosphate shunt regulated

Answer 5

Glucose 6 phosphate dehydrogenase initiates this pathway and comprises the rate limiting and only regulated step in the whole pathway
G6PD is feedback inhibited by NADPH would competes directly with NADP+for the enzyme active site therefore the NADPH/NADP+ ratio ensures that the cell only produces the needed amount of NADPH

Question 6

How does insulin regulate

Answer 6

UpRegulates the expression of the gene G6PD and flux to the pathway increases the absorptive state

Question 7

What are the products of HMS

Answer 7

Ribose 5 P

NADPH

Question 8

What is the importance of ribose 5P

Answer 8

Has 2 potential fates:
substrate for the synthesis of nucleotides: it produces the ribose sugar back bone
conversion through multiple steps to glycolytic intermediates

Question 9

What is the importance of NADPH

Answer 9

Reductive biosynthesis
Hydrogen peroxide reduction
Role in white blood cells
Role in nitric oxide synthesis
Role in cytochrome P450 mono oxygenase system

Question 10

What does NADPH do in reductive biosynthesis

Answer 10

Production of fatty acids in liver, adipose tissue and the mammary gland cholesterol in liver
and steroid hormones in the placenta ovaries testis and adrenal cortex

Question 11

What does hydrogen peroxide do

Answer 11

Can cause peroxidation of lipids present in cell membranes such as RBCs membrane causing the destruction damage of cell membrane and hemolysis

Question 12

What is reduced glutathione

Answer 12

Tripeptide Thiol present in most cells and chemically detoxify hydrogen peroxide

Question 13

What catalyzes the reaction of detoxification of hydrogen peroxide

Answer 13

Glutathione peroxidase

Question 14

What catalyzes the reaction of regeneration of GSH

Answer 14

Glutathione reductase using NADPH as a source of reducing equivalents

Question 15

What are additional enzymes that catalyze the conversion of other ROS to harmless products

Answer 15

Superoxide dismutase and Catalase

Question 16

What is the role of NADPH in white blood cells

Answer 16

After internalization of a microorganism has occurred in a white blood cell NADPH oxidase located in the leukocytes cell membrane is activated
this enzyme uses NADPH to reduce O2 from surrounding so superoxide anion in this case superoxide is used by the human body to kill the bacteria cell

Question 17

What is the respiratory burst

Answer 17

the rapid consumption of O2 that accompanies formation of is referred to as the respiratory burst

Question 18

What is the role of NADPH in nitric oxide synthesis

Answer 18

Synthesis of nitric oxide requires amino acid arginine O2 and NADPH as substrates and is catalyzed by Nitric oxide synthase enzyme

Question 19

What is the importance of nitric oxide

Answer 19

Recognized as a mediator in a broad area of biologic systems
it is endothelium derived and acts as a relaxing factor that causes vasodilation by relaxing vascular smooth muscle
it also acts as a neurotransmitter prevents platelet aggregation
and plays a role in macrophage function

Question 20

What is the rule of NADPH in cytochrome P450 Monooxygenese system

Answer 20

Monooxygenases incorporate one atom from O2 in to a substrate with the other atom being reduced to water
in the cytochrome P4 50 mono oxygenase system NADPH provides the reducing equivalents required by this series of reactions

Question 21

What is the importance of the cytocolm P450 mono oxygenase system

Answer 21

Helps the human body detoxify harmful agents such as drug food preservatives and others

Question 22

What is G6PD deficiency (favism)

Answer 22

▪️X-linked hereditary condition resulting from different point mutations in the gene coding for G6PD
▪️Most common disease producing enzyme abnormality in humans
▪️Characterized by hemolytic anemia caused by the inability to detoxify oxidizing agents
▪️Neonatal jaundice appearing 1 to 4 days after birth
▪️Confer resistance to malaria

Question 23

What is the pathogenesis of favism

Answer 23

Diminished G6PD activity improve the ability of the cell to form NADPH which is essential for the maintenance of the GSH pool
this result in a decrease in a detoxification of free radicals and peroxide formed within the cell
hence damaging the lipids in RBCs membrane resulting in hemolysis

Question 24

What does the oxidation of sulfhydryl group lead to

Answer 24

Formation of denatured proteins that form inside of a masses called Heinz bodies that attach to RBCs membranes

Question 25

What causes RBCs to be rigid

Answer 25

Oxidation of membrane proteins and they are removed from the circulation by macrophages in the spleen and liver

Question 26

What are the precipitating factors in G6PD deficiency

Answer 26

1-Oxidant drugs:
Antibiotics,anti malarials, anti pyretics
2-favism: Mediterranean variant are particularly is susceptible to the hemolyticeffect of the fava
not observed in all individuals with G6PD
3-Infection:infection is the most precipitating factor for hemolysis in G6PD deficiency the inflammatory response to infection results in the generation of free radicles in macrophages
the radicals can diffuse in to the RBC and cause oxidative damage

Question 27

What is the main aim of the uronic acid pathway

Answer 27

Production of glucoronic acid

Question 28

What are the sources of glucornic acid

Answer 28

Obtained in small amounts from diet and from lysosomal degradation of GAG

Question 29

What happens in the uronic acid pathway

Answer 29

Glucose 1 phosphate reacts with uridine triphosphate and it’s converted to UGP glucose
Oxidation of UGP glucose produces UDP glucuronic acid
End product of Glucoronic acid metabolism in humans is D-xylulose 5 phosphate
Which can enter the pentose phosphate pathway and produce the glycolytic intermediates glyceraldehyde 3 phosphate and fructose 6 phosphate

Question 30

What is the importance of uronic acid pathway

Answer 30

1-Synthesis of Glucoronic acid which is used in conjugation of many steps as a step of detoxification of such agents
One of those agents is bilirubin this helps excretion of living in urine and prevents development of jaundice
2-Synthesis of GAG‘s proteoglycans and glucuronides