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Lehninger Principles of Biochemistry Overview

Introduction to Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway

Glycolysis is a central pathway in cellular metabolism that involves breaking down glucose into pyruvate, producing ATP and NADH in the process. This pathway occurs in the cytosol and comprises a series of ten enzymatic reactions. Its significance extends beyond energy production, as it plays a crucial role in various biosynthetic processes.

Glycolysis Overview

Glycolysis is divided into two main phases: the preparatory phase and the payoff phase.

Preparatory Phase

The preparatory phase includes the first five steps of glycolysis where glucose is phosphorylated and converted into fructose 1,6-bisphosphate.

  1. Hexokinase Reaction: Glucose is phosphorylated to form glucose 6-phosphate through the action of the enzyme hexokinase, utilizing one ATP molecule. The reaction can be summarized as:
    ext{Glucose} + ext{ATP}
    ightarrow ext{Glucose 6-phosphate} + ext{ADP}
    The free energy change for this reaction, $ ext{AG'}^{ ext{°}}$, is approximately -33.4 kJ/mol, indicating it is highly favorable.

  2. Phosphohexose Isomerase Reaction: Glucose 6-phosphate is isomerized to fructose 6-phosphate via the enzyme phosphohexose isomerase.

  3. Phosphofructokinase Reaction: The key regulatory step occurs here, where fructose 6-phosphate is phosphorylated by phosphofructokinase-1 (PFK-1) to form fructose 1,6-bisphosphate, using another ATP molecule with an $ ext{AG'}^{ ext{°}}$ of approximately -14.2 kJ/mol, reinforcing its regulatory role.

  4. Aldolase Reaction: Fructose 1,6-bisphosphate is cleaved into two three-carbon molecules: glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The formation of these intermediates is crucial for the next steps in glycolysis.

  5. Triose Phosphate Isomerase Reaction: The dihydroxyacetone phosphate is converted into glyceraldehyde 3-phosphate, allowing for the continuation of glycolysis.

Payoff Phase

The payoff phase transforms glyceraldehyde 3-phosphate into pyruvate, generating ATP and NADH in the process.

  1. Glyceraldehyde 3-Phosphate Dehydrogenase Reaction: Glyceraldehyde 3-phosphate is oxidized and phosphorylated to form 1,3-bisphosphoglycerate. This step also generates NADH:
    ext{Glyceraldehyde 3-phosphate} + ext{NAD}^+ + ext{Pi}
    ightarrow 1,3- ext{bisphosphoglycerate} + ext{NADH} + ext{H}^+

  2. Phosphoglycerate Kinase Reaction: This is the first ATP-generating step through substrate-level phosphorylation where 1,3-bisphosphoglycerate is converted to 3-phosphoglycerate, producing ATP:
    1,3- ext{bisphosphoglycerate} + ext{ADP}
    ightarrow 3- ext{phosphoglycerate} + ext{ATP}

  3. Phosphoglycerate Mutase Reaction: 3-phosphoglycerate is rearranged to become 2-phosphoglycerate.

  4. Enolase Reaction: 2-phosphoglycerate is dehydrated to form phosphoenolpyruvate (PEP).

  5. Pyruvate Kinase Reaction: The final step in glycolysis where PEP is converted into pyruvate, yielding another molecule of ATP:
    ext{Phosphoenolpyruvate} + ext{ADP}
    ightarrow ext{Pyruvate} + ext{ATP}
    This reaction has a large negative $ ext{AG'}^ ext{°}$ and is thus thermodynamically favorable, driving glycolysis to completion.

Net Yield of Glycolysis

The net yield of glycolysis from one glucose molecule is:

  • 2 Pyruvate

  • 2 ATP (net gain; 4 produced, 2 used)

  • 2 NADH

Gluconeogenesis Overview

Gluconeogenesis is the metabolic pathway that generates glucose from non-carbohydrate precursors like pyruvate, lactate, and certain amino acids. This process is crucial during fasting, exercise, and when carbohydrate intake is insufficient.

  • Key regulatory enzymes include pyruvate carboxylase and phosphoenolpyruvate carboxykinase, which convert pyruvate into phosphoenolpyruvate, effectively reversing the pyruvate kinase step in glycolysis.

  • It is an energy-consuming process, using ATP and GTP.

Pentose Phosphate Pathway

The pentose phosphate pathway serves as an alternative to glycolysis, generating NADPH and ribose-5-phosphate. It is vital for anabolic reactions, including fatty acid and nucleic acid synthesis.

  • It consists of an oxidative phase that generates NADPH and a non-oxidative phase responsible for the interconversion of sugars.

This pathway plays a significant role in cellular redox balance and biosynthetic pathways.