Pentose Phosphate Pathway P P P Hexose mono

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Pentose Phosphate Pathway P. P. P (Hexose mono phosphate shunt) H. M. S Almoeiz

Pentose Phosphate Pathway P. P. P (Hexose mono phosphate shunt) H. M. S Almoeiz Yousif Thursday, October 29, 2020 1

Definition • Groups of reactions found in cytosol work to utilize 3 moles of

Definition • Groups of reactions found in cytosol work to utilize 3 moles of glucose 6 P • To give : -2 moles of glucose 6 P -Ribose 5. P -NADPH, CO 2, glyceraldehyde 3 P. Thursday, October 29, 2020 2

Location liver Testis. Location cytosol of Mammary glands Thursday, October 29, 2020 Adipose tissues

Location liver Testis. Location cytosol of Mammary glands Thursday, October 29, 2020 Adipose tissues RBCs 3

• Function 1. NADPH production 2. Ribose synthesis Reducing power carrier • Synthetic

• Function 1. NADPH production 2. Ribose synthesis Reducing power carrier • Synthetic pathways Role as cellular antioxidants Thursday, October 29, 2020 Nucleic acids & nucleotides 4

Demand for NADPH • Biosynthetic pathways • FA synthesis (liver, adipose, mammary) • Cholesterol

Demand for NADPH • Biosynthetic pathways • FA synthesis (liver, adipose, mammary) • Cholesterol synthesis (liver) • Steroid hormone synthesis (adrenal, ovaries, testes) • Reduced glutathione as an antioxidant (RBC) Thursday, October 29, 2020 5

Thursday, October 29, 2020 6

Thursday, October 29, 2020 6

Characteristics: • P. P. P divided into two phases: • 1. phase one ,

Characteristics: • P. P. P divided into two phases: • 1. phase one , oxidative , irreversible phase. • 2. phase two , non oxidative , reversible phase. Thursday, October 29, 2020 7

phase one • Oxidative phases • Reactions producing NADPH • Irreversible Thursday, October 29,

phase one • Oxidative phases • Reactions producing NADPH • Irreversible Thursday, October 29, 2020 8

phase two • Non-oxidative phases • Produces ribose-5 -P • Reversible reactions feed to

phase two • Non-oxidative phases • Produces ribose-5 -P • Reversible reactions feed to glycolysis Thursday, October 29, 2020 9

NADPH producing reactions • Glucose-6 -P dehydrogenase • 6 -P-gluconate dehydrogenase Thursday, October 29,

NADPH producing reactions • Glucose-6 -P dehydrogenase • 6 -P-gluconate dehydrogenase Thursday, October 29, 2020 10

Regulation • Glucose-6 -P dehydrogenase • First step • Rate limiting • Allosteric Regulation

Regulation • Glucose-6 -P dehydrogenase • First step • Rate limiting • Allosteric Regulation • Feedback inhibited by NADPH • Inducible enzyme • Induced by insulin Thursday, October 29, 2020 11

Role of NADPH in the RBC • Production of superoxide • Hb-Fe 2+-O 2

Role of NADPH in the RBC • Production of superoxide • Hb-Fe 2+-O 2 -> Hb-Fe 3+ + O 2 -. • O 2 -. + 2 H 2 O -> 2 H 2 O 2 • Both O 2 -. & H 2 O 2 can produce reactive free radical species, damage cell membranes, and cause hemolysis Thursday, October 29, 2020 12

Detoxification of Superoxide Anion and Hydrogen Peroxide • Antioxidant enzymes • Superoxide dismutase •

Detoxification of Superoxide Anion and Hydrogen Peroxide • Antioxidant enzymes • Superoxide dismutase • Glutathione peroxidaes • Glutathione reductase Thursday, October 29, 2020 13

G 6 PDH Deficiency and Hemolytic Anemia • Most common genetic enzymopathy • Mediterranean,

G 6 PDH Deficiency and Hemolytic Anemia • Most common genetic enzymopathy • Mediterranean, Asian, African descent • Recessive sex-linked mutation • X-chromosome • Rare in females (two X-chromosomes) Thursday, October 29, 2020 14

G 6 PD Deficiency • Exposure to anti-malarial drugs (Primaquine) results in increased cellular

G 6 PD Deficiency • Exposure to anti-malarial drugs (Primaquine) results in increased cellular production of superoxide and hydrogen peroxide (Primaquine sensitivity) • Other chemicals known to increase oxidant stress • Sulfonamides (antibiotic) • Asprin and NSAIDs • Fava beans Thursday, October 29, 2020 15

Case Study • 21 Y. O male medical student with malaria • Treated with

Case Study • 21 Y. O male medical student with malaria • Treated with primaquine • Four days later: • Black colored urine • Low RBC count • Elevated reticulocyte count • Low hemoglobin • Elevated serum bilirubin • Pt recovered in a few days Thursday, October 29, 2020 16

Symptoms • Black colored urine • Hemolysis may result in urinary excretion of hemoglobin

Symptoms • Black colored urine • Hemolysis may result in urinary excretion of hemoglobin • Low RBC count & low hemoglobin • Result of high rate of hemolysis • Elevated bilirubin • Catabolism of heme Thursday, October 29, 2020 17

Defective G 6 PDH • Results in enzyme with unstable structure • Patient with

Defective G 6 PDH • Results in enzyme with unstable structure • Patient with 10% of normal activity Enough to generate NADPH under normal condition • Newly made RBCs have normal 6 PDH activity • Patients recover quickly (8 days) Thursday, October 29, 2020 18

Carbohydrate Metabolism Thursday, October 29, 2020 19

Carbohydrate Metabolism Thursday, October 29, 2020 19

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