19 - Pentose phosphate pathway (PPP) of glucose metabolism – importance for the metabolism, chemical reactions, regulation. Role of PPP in the red blood cells. Enzymopathies: Glucose-6 phosphate dehydrogenase deficiency.

section

• what is ppp

• 2 phases of ppp

• oxidative phase

• non-oxidative phase

• importance of NADPH

• Glucose -6-phosphate deficiency

• PPP

• what is ppp

• alternative pathway when ATP doesn’t need to be produced

• occurs in cytoplasm

• 2 phases of ppp

• Oxidative

  • NADPH (not reversible reaction) → functions:

    • electron donor

    • anabolic reaction

    • antioxidant molecules

• Non-oxidative

  • Ribose-5-phosphate (reversible) → function:

  • makes nucleotides for DNA or RNA synthesis

• oxidative phase

1. glucose-6-phosphate undergoes oxidation to form → 6-phosphoglucono delta lactone , reducing NADP+ to NADPH using glucose 6-phosphate dehydrogenase

2. 6-phsophoglucono delta lactone undergoes hydrolysis to form → 6 phosphogluconate, using gluconolactonase

3. 6-phsophogluconate undergoes decarboxylation and a C atom is cleaved to form → ribulose-5-phosphate, reducing NADP+ to NADPH, using 6-phsophogluconate dehydrogenase

• non-oxidative phase

• importance of NADPH

• donate electrons in anabolic pathways

• fatty acid synthesis

• steroid hormone synthesis

• cholesterol synthesis

• Glucose -6-phosphate deficiency

• impairment of NADPH production, detoxification of H2O2 is inhibited causing cellular damage

• lipid peroxidation → erythrocyte membrane breakdown and hemolytic anaemia

• Individuals with G6PD deficiency = asymptomatic

• PPP

process - ppp

substrate - glucose-6-phsophate

products - NADP + pentoses

enzyme - glucose-6-p DH, 6-p-gluconate DH, cofactor NADP , insulin activates ATP/ADP

localisation - cytoplasm

energy balance -

deficiency - glucose-6-p DH deficiency, hemolysis

role - source ribose-5-p + NADPH