stryer_biochem10e_lectureslides_ch16

Chapter 16: Glycolysis and Gluconeogenesis

Overview of Glycolysis and Gluconeogenesis

  • Glycolysis:

    • Sequence of reactions converting one molecule of glucose into 2 molecules of pyruvate with the net production of 2 ATP.

    • An anaerobic process; does not require oxygen.

    • It is common in both prokaryotic and eukaryotic cells.

  • Gluconeogenesis:

    • Synthesis of glucose from non-carbohydrate precursors (e.g., lactate, amino acids).

    • Prominent during fasting and starvation.

Metabolic Pathways

Key Products of Glycolysis

  • Starting from Glucose:

    • Produces Pyruvate or Lactate depending on the presence of oxygen.

    • Can lead to the production of CO2 and H2O via complete oxidation.

Detailed Pathway of Glycolysis

Main Steps and Reactions

  • Stage 1: Traps glucose and prepares it for cleavage, does not generate ATP:

    1. Hexokinase phosphorylates glucose to glucose-6-phosphate (G6P).

    2. Phosphoglucose isomerase converts G6P to fructose-6-phosphate (F6P).

    3. Phosphofructokinase (PFK) phosphorylates F6P to fructose-1,6-bisphosphate (F1,6BP).

    4. Aldolase cleaves F1,6BP into glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP).

  • Stage 2: Converts three-carbon sugars to pyruvate, generating ATP:

    1. Glyceraldehyde 3-phosphate dehydrogenase converts GAP to 1,3-bisphosphoglycerate (1,3-BPG).

    2. Phosphoglycerate kinase transfers the phosphoryl group from 1,3-BPG to ADP to form ATP and 3-phosphoglycerate.

    3. Enolase converts 2-phosphoglycerate to phosphoenolpyruvate (PEP).

    4. Pyruvate kinase transfers a phosphoryl group from PEP to ADP to generate pyruvate and ATP.

Energetics of Glycolysis

  • Glycolysis results in a net gain of 2 ATP and the energy released is approximately −90 kJ mol−1.

Transport of Glucose

  • Monosaccharides are actively transported into intestinal endothelial cells, then passively transported into the bloodstream and cells.

  • GLUT Transporters facilitate glucose movement across membranes (GLUT1 to GLUT5).

    • GLUT1: Basic uptake in all tissues.

    • GLUT4: In muscles, amount increases with endurance training.

Regulation of Glycolysis

  • Regulation relies on energy status, primarily the ATP/AMP ratio and feedback from glycolytic intermediates.

    • PFK is allosterically inhibited by ATP and activated by AMP.

    • Hexokinase is inhibited by its product G6P.

    • Pyruvate kinase is inhibited by ATP and alanine.

Gluconeogenesis Pathway

  • Begins with the conversion of Pyruvate to Phosphoenolpyruvate (PEP), which requires pyruvate carboxylase and PEPCK (phosphoenolpyruvate carboxykinase).

  • Involves bypassing three irreversible steps of glycolysis:

    • Fructose 1,6-bisphosphatase catalyzes the conversion of F1,6BP to F6P.

    • Glucose-6-phosphatase converts G6P to glucose, primarily in the liver.

Phenomena in Glycolytic Regulation

  • Cori Cycle: Lactate from muscles can be converted to glucose in the liver.

  • Bifunctional enzymes like PFK2 and FBPase2 regulate the levels of fructose-2,6-bisphosphate, influencing glycolytic and gluconeogenic flux.

Disorders Related to Glycolysis and Gluconeogenesis

  • Deficiency in enzymes involved in glycolysis/gluconeogenesis can lead to metabolic disorders (e.g., Pyruvate carboxylase deficiency results in hypoglycemia and lactic acidosis).

  • Triose phosphate isomerase deficiency (TPID) shows symptoms linked to metabolite accumulation affecting various body systems.

Evolutionary Insights

  • Glycolytic enzymes demonstrate an intricate evolutionary development, showing distinct variations in amino acid structure while performing similar functions.