Pentose Phosphate Pathway

Carbohydrate Metabolism

Overview

  • Glycogen (Polysaccharide) Metabolism

    • Glycogen breakdown (catabolism)

    • Glycogen synthesis (anabolism)

  • Glucose (Monosaccharide) Metabolism

    • Glucose breakdown (catabolism)

    • Glycolysis

    • Citric Acid Cycle

    • Pentose Phosphate Pathway

    • Glucose synthesis (anabolism)

    • Gluconeogenesis

    • Photosynthesis

      • Light reaction

      • Dark reaction - Calvin cycle

Pentose Phosphate Pathway

General Description

  • The Pentose Phosphate Pathway (PPP) is an alternate route for the oxidation of glucose.

  • Purpose:

    • To generate NADPH and metabolize 5-carbon sugars.

  • Main Products:

    • NADPH:

    • Acts as an electron donor, crucial for:

      • Reductive biosynthesis of fatty acids and steroids.

      • Repair of oxidative damage.

    • Ribose 5-Phosphate (R-5-P):

    • A biosynthetic precursor of nucleotides.

    • Used in DNA and RNA synthesis.

    • Necessary for the synthesis of some coenzymes.

Phases of the Pentose Phosphate Pathway

  • The reactions of the pentose phosphate pathway occur in the cytosol and comprise two distinct phases:

    1. Oxidative Phase

    2. Nonoxidative Phase

1. Oxidative Phase

  • Generates NADPH and ribulose 5-phosphate.

  • Process:

    • Glucose 6-phosphate undergoes dehydrogenation and decarboxylation to yield ribulose 5-phosphate (a pentose), which can be converted to its isomer, ribose 5-phosphate.

  • First Reaction:

    • Catalyzed by glucose-6-phosphate dehydrogenase, this step is the rate-limiting step and functions as the control site for the PPP.

    • Key Enzyme Involvement:

    • NADP+ is used as a hydrogen acceptor because the affinity (KM) of glucose-6-phosphate dehydrogenase for NADP+ is a thousand times lower than for NAD+.

  • Overall Reaction of 1st Phase:
    extGlucose6−phosphate+2extNADP++extH<em>2extOightarrowextribulose5−phosphate+2extNADPH+2extH++extCO</em>2ext{Glucose 6-phosphate} + 2 ext{NADP}^+ + ext{H}<em>2 ext{O} ightarrow ext{ribulose 5-phosphate} + 2 ext{NADPH} + 2 ext{H}^+ + ext{CO}</em>2

2. Nonoxidative Phase

  • Involves the interconversion of 3-, 4-, 5-, 6-, and 7-carbon sugars through a series of non-oxidative reactions.

  • Key Enzymes:

    • Transketolase: Transfers 2-C units.

    • Transaldolase: Transfers 3-C units.

  • Flow of Carbon Atoms:

    • The balance sheet below summarizes the flow of 15 C atoms through PPP reactions wherein 5-C sugars convert into 3-, 4-, 5-, 6-, and 7-carbon sugars:

    • C<em>5+C</em>5<br>ightleftharpoonsC<em>3+C</em>7ext(Transketolase)C<em>5 + C</em>5 <br>ightleftharpoons C<em>3 + C</em>7 ext{ (Transketolase)}

    • C<em>3+C</em>7<br>ightleftharpoonsC<em>6+C</em>4ext(Transaldolase)C<em>3 + C</em>7 <br>ightleftharpoons C<em>6 + C</em>4 ext{ (Transaldolase)}

    • C<em>4+C</em>5<br>ightleftharpoonsC<em>6+C</em>3ext(Transketolase)C<em>4 + C</em>5 <br>ightleftharpoons C<em>6 + C</em>3 ext{ (Transketolase)}

    • Net Reaction:

    • 3C<em>5ightleftharpoons2C</em>6+C33 C<em>5 ightleftharpoons 2 C</em>6 + C_3

  • Regeneration of Glucose-6-Phosphate:

    • Glucose-6-phosphate can be regenerated from either 3-C glyceraldehyde-3-phosphate or 6-C fructose-6-phosphate through gluconeogenesis enzyme activities.

  • Isomerization:

    • Ribulose 5-phosphate generated during the oxidative phase can be isomerized into ribose 5-phosphate, which is critical for nucleotide synthesis.

Regulation of the Pentose Phosphate Pathway

  • The entry of glucose 6-phosphate into the pentose phosphate pathway is regulated by glucose-6-phosphate dehydrogenase, the key regulatory enzyme.

  • Factors Influencing Regulation:

    • NADPH is a strong inhibitor of glucose-6-phosphate dehydrogenase, while NADP+ competes with NADPH at the enzyme's active site.

    • The balance of NADPH/NADP+ affects enzyme activity:

    • If NADPH/NADP+ increases, enzyme activity is inhibited.

    • If NADPH/NADP+ decreases, enzyme activity is activated.

  • Synthesis Induction:

    • The synthesis of glucose-6-phosphate dehydrogenase is induced by an increased insulin/glucagon ratio following a high-carbohydrate meal, facilitating the conversion of glucose into polysaccharides and subsequently to NADPH.