Course: Nutrition and Metabolism

Transcription

1 Course: Nutrition and Metabolism Part (1): Metabolism of Carbohydrates Lecture (8): Pentose Phosphate Pathway Dr. Rihab Siddig Mobile:

2 Glucose Uses Energy Stores Glycogen Glucose Pentose Phosphate Pathway Ribose-5-phosphate & NADPH Glycolysis Pyruvate

3 Definition Pathway that uses glucose to form ribose sugar and NADPH. No ATP is liberated

4 Organs with Active Pentose Phosphate Pathway RBCs liver lactating mammary glands adipose tissue adrenal cortex testis thyroid gland

5 Cellular Site of PPP Within the cell, this pathway takes place in the cytoplasm.

6 Functions of PPP Produces 1. Ribose 5-phosphate 2. NADPH

7 Functions of Products of PPP 1) Ribose 5-phosphate used for synthesis of nucleic acids 2) NADPH used for Synthesis of lipids Removal of strong oxidants ( H )

8 Pentose Phosphate Pathway Reactions The pentose phosphate pathway has two phases Oxidative phase. non-oxidative phase.

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10 Oxidative Phase Irreversible reactions G 6-P Ribulose 5-P

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12 G-6-P DH Reaction

13 Lactonase Reaction

14 6-phosphogluconate DH Reaction

15 Oxidative Nonreversible Phase Irreversible reactions G 6-P Ribulose 5-P 2NADPH is produced ICO 2 is produced

16 Reversible reactions gives ribose-5-phosphate. Rib 5-P 2 F 6-P + G 3-P Thiamine is needed

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18 Ribulose-5-phosphate Isomerase Reaction

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20 Ribulose 5-Phosphate Epimerase Reaction

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22 transfers 2 carbon groups from a ketose to aldose TK

23 Transketolase: catalyzes the transfer of C2 units the ketose which donates the 2 carbons becomes aldose and the aldose which accepts the two carbons becomes ketose.

24 Thiamin as a Coenzyme Transketolase requires thiamine diphosphate (TDP) as a co-enzyme.

25 Transaldolase transfers 3 carbon groups in the same way done by transketolase. TA

26 Transaldolase: catalyzes the transfer of C3 units

27 Transketolases and Transaldolases Both are reversible reactions TK TA

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29 CH 2 OH C=O CH 2 OH C=O HO-C C-OH CH 2 OP + CHO C-OH C-OH C-OH CH 2 OP HO-C C-OH C-OH C-OH CH 2 OP Xyulose-5-PO 4 Ribose-5-PO 4 Sedoheptulose-7-PO 4 CHO C-OH CH 2 OP Transketolase Glyceraldehyde-3-PO 4

30 CHO C-OH CH 2 OP + Glyceraldehyde-3-PO 4 HO-C Sedoheptulose-7-PO 4 CH 2 OH C=O C-OH C-OH C-OH CH 2 OP CHO C-OH C-OH CH 2 OP CH 2 OH C=O HO-C C-OH C-OH CH 2 OP Fructose-6-PO 4 Transaldolase Erythrose-4-PO 4

31 CH CHO 2 OH C-OH C=O CHO C-OH + HO-C C-OH + CH 2 OP C-OH CH 2 OP CH 2 OP Glyceraldehyde- 3-PO Erythrose-4-PO Xylulose-5-PO CH 2 OH C=O HO-C C-OH C-OH CH 2 OP Fructose-6-PO 4 Transketolase

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33 The F6P can be recycled into the pathway in the form of G6P, which enters PPP again.

34 Why Two phases? Oxidative For NADPH requiring cells e.g. RBCs Non-oxidative For cells that need ribose for DNA and RNA

35 The Pentose Phosphate Pathway in RBCs Erythrocytes depend on the PPP for NADPH, which reduces glutathione. Reduced glutathione is needed to maintain the RBC membrane.

36 Glutathione is a Tripeptide Gly Gly Gly Cys SH Cys S S Cys + H 2 O Glu Glu Glu Reduced form of glutathione (active) Oxidized form of glutathione (inactive)

37 Function of glutathione Glutathione eliminates H 2 O 2 formed in RBCs H 2 O 2 destroys the cell membrane

38 H 2 O 2 glutathione peroxidase 2 H 2 O 2 GSH glutathione reductase GSSG NADP + NADPH + H + pentose pathway. Reactions of glutathione reduction and oxidation

39 NADPH is the coenzyme of glutathione reductase to keep the glutathione reduced; H 2 O 2 2GSH NADP + glutathione reductase 2H 2 O G-S-S-G NADPH + H +

40 G-6-P Dehydrogenase Deficiency Deficiency of glucose 6-phosphate dehydrogenase results in hemolytic anemia. It is a genetic disease found in more than 100 million people in the world

41 In people with G6PDH Deficiency Some drugs (e.g., aspirin and primaquine) can cause increased H 2 O 2 production. This leads to damage in membranes leading to hemolytic anemia. Also fava beans produce lots of H 2 O 2

42 Disease Also called Favism

43 Protective Role of NADPH

44 Regulation of PPP The regulatory enzyme is G-6-P DH Insulin activates it in the fed state

45 Questions?