Pentose Phosphate Pathway: Functions, Regulation, and G6PD Deficiency, Essays (high school) of Biology

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Pentose Phosphate Pathway (PPP)

Hexose Monophosphate Pathway (HMP) Hexose Monophosphate Shunt (HMS) or 6-Phosphogluconate Pathway

• (^) Primary functions of pathway
  • (^) Production of NADPH
  • (^) Production of Pentoses
  • (^) Disposal of Pentoses
• (^) Oxidative branch
  • Glucose 6-phosphate dehydrogenase regulation
• (^) Non-oxidative branch
  • (^) Transketolase
  • (^) Transaldolase
• (^) Functions of NADPH
  • (^) Synthesis of fatty acids, steroids, etc.
  • (^) Conversion of Ribonucleotides to Deoxyribonucleotides
  • Phagocytosis
  • (^) NO synthesis
  • (^) Reduction of reactive oxygen species with glutathione
• (^) Genetics of G6PDH mutations

Outline

Primary Functions of the Pathway

1. To generate reducing equivalents, in the form of NADPH.
2. To provide the cell with ribose 5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids.
3. Although not a significant function of the pathway, it can operate to metabolize dietary pentose sugars.

Sites of the pathway

1. Tissues: Present in essentially all cells. Liver, adipose tissue, adrenal cortex, testis and lactating mammary gland utilize large amounts of NADPH for the synthesis of fatty acids and steroids.
2. Erythrocytes utilize the reactions of the PPP to generate large amounts of NADPH used in the reduction of glutathione.

Pentose Phosphate Pathway (PPP, HMP) Occurs in 2 stages:

1. Oxidative reactions: a. The initial reactions of the PPP that result in the synthesis of ribulose 5-phosphate b. Leads to generation of 2 molecules of NADPH per molecule of Glucose 6-phosphate

1. Oxidative reactions

2. Non-oxidative reactions a. Are a series of sugar interconversion reactions. b. No NADPH is generated. c. Result in the conversion of ribulose 5-phosphate to mainly: i. ribose 5-phosphate: in rapidly dividing cells with active nucleic acid synthesis, or ii. Intermediates of glycolysis: in non-dividing cells.

Transfers 2 carbons Transfers 3 carbons

2. Non-oxidative reactions

Transketolase

1. Like other enzymes that transfer similar carbon groups, transketolase requires thiamine pyrophosphate (TPP) as a co-factor.
2. The blood levels of active transketolase are used in the clinical laboratory to assess Thiamine levels and to establish a diagnosis of deficiency state (Beriberi). 2. Non-oxidative reactions

Pentose Phosphate Pathway. Relationship to Glycolysis

• (^) In actively growing cells (making DNA and RNA), both the oxidative and non-oxidative pathways are active.
• (^) In cells that need ribose but not NADPH, only the non-oxidative pathway is functioning. - (^) In cells like rbc that need only NADPH, the non-oxidative pathway is functioning only to process the carbons atoms back to glycolytic intermediates. 14

5. The reduction of hydrogen peroxide and other reactive oxygen species in: a. the RBCs (glutathione, i.e., -glutamyl- cysteinyl-glycine). Erythrocytes utilize the reactions of the PPP to generate large amounts of NADPH used in the reduction of glutathione. b. Liver. (microsomal cytochrome P- mono-oxygenase system) c. the lysis of bacteria.

Functions of NADPH

Reduction of Glutathione: Glutathione in cells can detoxify hydrogen peroxide and lipid peroxides using the selenium enzyme glutathione peroxidase.

Antioxidants and Reactive Oxygen Species (ROS)

• (^) Even though molecular oxygen is relatively inert, partial reduction by various biological systems results in the activation of oxygen to form the superoxide radical and hydrogen peroxide

Antioxidants and the Family of Reactive Oxygen Species (ROS)

• (^) The ROS are formed continuously in the RBCs and other cells .