BIOL 304 - Chapter 20 Pentose Phosphate Pathway

Pentose phosphate pathway

pathways generating a crucial source of NADPH for use in reductive biosynthesis and for protection against oxidative stress

where does PPP occur?

cytoplasm

phase 1 of PPP

Oxidative regeneration of NADPH

Glucose 6-phosphate is oxidized to ribulose 5-phosphate

phase 2 of PPP

Nonoxidative interconversion of 3, 4, 5, 6, 7 carbon sugars

Interconversions rely on same reactions leading to regeneration of R1,5-BP in the Calvin-Benson Cycle

glucose 6-dehydrogenase

catalyzes the first step, leading to NADP+ to form NADPH and H+

transketolase, transaldolase, and phosphopentose epimerase

can create different carbon molecules in step 2

The fate of G6-P is controlled by

the cytoplasmic concentration of NADP+ (rate determining step) - irreversible

Low levels of NADP+

limit dehydrogenation of G6-P because it is needed as the electron acceptor

Ensures NADPH is not generated unless needed for reductive biosynthesis or protection against oxidative stress

mode 1 of PPP

much more ribose 5-phosphate than NADPH is required

G6-P is converted into F6-P and GA3-P by glycolytic pathway

Transaldolase and transketolase convert 2 molecules of F6-P and one molecule of GAP into 3 molecules of ribose 5-phosphate

mode 2 of PPP

 needs of ribose 5-phosphate and NADPH are balanced

G6-P is processed to 1 molecule of ribulose 5-phosphate while generating 2 molecules of NADPH

Ribulose 5-phosphate is converted into ribose 5-phosphate

mode 3 of PPP

much more NADPH than ribose 5-phosphate is required

G6-P is completely oxidized to CO2 through 3 groups of reactions

• Oxidative phase of PPP forms 2 molecules of NADPH and 2 molecules of ribulose 5-phosphate 

• Ribulose 5-phosphate is converted into F6-P and GAP by transketolase and transaldolase

• G6-P is resynthesized from fructose

mode 4 of PPP

both NADPH and ATP are required

• Ribulose 5-phosphate formed from G6-P can be converted into pyruvate

• F6-P and GAP derived from ribose 5-phosphate enter the glycolytic pathway rather than reverting to G6-P

• Pyruvate formed can be oxidized to generate more ATP or used as a building block in a variety of biosynthesis

Rapidly Dividing Cells

• Require ribose 5-phosphate for nucleic acid synthesis

• NADPH for fatty acid and membrane lipid synthesis

• Switch to aerobic glycolysis to meet ATP needs

• Divert G6-P and glycolytic intermediates to the nonoxidative phase of PPP to generate NADPH and ribose 5-phosphate

Reduced glutathione (GSH)

a tripeptide with a free sulfhydryl group that combats oxidative stress by reducing ROS to harmless forms

Serves as sulfhydryl buffer that keeps residues of hemoglobin in reduced sulfhydryl form

Without adequate levels of GSH

hemoglobins cross-link with one another to form aggregates (Heinz bodies) on cell membranes

Membranes damaged by Heinz bodies and reactive oxygen species become deformed → cells undergo lysis

Oxidative glutathione (GSSG)

must be reduced to regenerate GSH

Reducing power is supplied by

• NADPH generated by glucose 6-phosphate dehydrogenase in the PPP

Glucose 6-phosphate dehydrogenase deficiency

characterized by 10-fold reduction in enzymatic activity in RBCs

Protects against malaria

• Parasites causing malaria require NADPH for growth and infection induces oxidative stress in infected human cells

• Since PPP is compromised, cells and parasite die from oxidative damage