biochem final pt 2 PPP NADPH NADH GSH OXIDATIVE STRESS

Purpose of the Pentose Phosphate Pathway (PPP)

To produce NADPH and ribose-5-phosphate for biosynthesis and antioxidant defense

Phases of PPP

1. Oxidative phase (irreversible) → makes NADPH and ribulose-5-phosphate; 2. Non-oxidative phase (reversible) → interconverts sugars

Key enzyme in oxidative phase of PPP

Glucose-6-phosphate dehydrogenase (G6PD)

Products of oxidative phase of PPP

NADPH and ribulose-5-phosphate

Products of non-oxidative phase of PPP

Ribose-5-phosphate, fructose-6-phosphate, and glyceraldehyde-3-phosphate

Main uses of NADPH

Reductive biosynthesis (fatty acids, cholesterol), antioxidant defense, glutathione regeneration, cytochrome P450 system

NADPH vs. NADH (primary function)

NADPH is used in biosynthesis and detox; NADH is used in energy production (ETC)

Tissues with active PPP

Liver, adipose tissue, adrenal glands, RBCs, rapidly dividing cells (high NADPH/nucleotide demand)

What is GSH?

Reduced glutathione — a tripeptide antioxidant (Glu-Cys-Gly) that neutralizes reactive oxygen species

How GSH reduces peroxides

GSH donates electrons to hydrogen peroxide via glutathione peroxidase → becomes oxidized glutathione (GSSG)

Reaction of GSH with H₂O₂

2 GSH + H₂O₂ → GSSG + 2 H₂O

How GSH is regenerated

GSSG is reduced back to GSH using NADPH via glutathione reductase

Why PPP is critical in RBCs

Provides NADPH to regenerate GSH and prevent oxidative damage → protects against hemolysis

G6PD Deficiency

A genetic disorder causing decreased NADPH production → impaired GSH regeneration → hemolytic anemia

Why NADPH is essential in liver

Supports detoxification via cytochrome P450 enzymes and conjugation reactions

Metabolic flexibility of PPP

Intermediates can be shunted into nucleotide synthesis or glycolysis depending on cellular needs