Topic 9

Topic 9: Carbohydrate Metabolism

Overview of Carbohydrates

• Carbohydrates are essential sources of energy and reducing power for cells.

• This topic focuses on glucose, particularly glucose-6-phosphate, and its metabolic fates.

Absorption and Transport of Glucose

• Glucose is absorbed from the digestive tract and enters circulation in the blood.

• It enters cells via glucose-specific transport proteins:

  • Some transporters utilize passive movement based on concentration gradients.

  • Others employ energy from sodium ion (Na+) gradients to symport glucose into cells.

Metabolism of Glucose Inside the Cell

• Upon entering the cell, glucose is quickly converted into glucose-6-phosphate.

• Glucose-6-phosphate has several metabolic pathways:

  • Glycogen synthesis and degradation

Glycogen Synthesis and Breakdown

• Glycogen is a polysaccharide made of glucose monomers, stored mainly in the liver and striated muscle.

Glycogen Synthesis

• Glucose-6-phosphate is converted to glucose-1-phosphate as the first step.

• The synthesis of glycogen involves:

  1. Conversion of glucose-1-phosphate into a glycogen chain through a two-step reaction that requires UTP:

  • ${Glycogen (n residues)}+{G1P}+{UTP}\to{Glycogen (n+1 residues)}+{UDP}+2{Pi}$

  1. The second step is catalyzed by the enzyme glycogen synthase.

• UTP hydrolysis is energetically similar to ATP hydrolysis, making the synthesis process favorable:

  • $ext{NTP} + ext{ADP} → ext{NDP} + ext{ATP}$

Glycogen Breakdown

• Glycogen phosphorylase catalyzes the removal of glucose monomers from glycogen, producing glucose-1-phosphate:

  • $ext{Glycogen (n residues)} + ext{Pi} → ext{Glycogen (n – 1 residues)} + ext{G1P}$

• The phosphate derived from inorganic phosphate (not ATP) aids in the breakdown process.

Regulation of Glycogen Metabolism

• Glycogen metabolism is controlled primarily through the phosphorylation states of glycogen synthase and phosphorylase:

  • Hormonal signals influence these phosphorylation states:

  • Insulin:

    • Promotes glycogen synthesis (dephosphorylates both enzymes).

  • Glucagon:

    • Stimulates glycogen breakdown in the liver only (phosphorylates these enzymes).

    • Liver releases glucose to maintain blood glucose levels.

  • Epinephrine:

    • Triggers phosphorylation of both enzymes in liver and skeletal muscle.

• Allosteric effectors also regulate glycogen metabolism:

  • Glycogen synthase is activated by glucose-6-phosphate.

  • Glycogen phosphorylase is activated by AMP and inhibited by ATP and glucose-6-phosphate.

  • The liver's glycogen phosphorylase is inhibited by glucose, reflecting cellular status.

Overview of Glycolysis

• Glycolysis occurs in the cytoplasm and is an oxidative process.

• Conversion of glucose to glucose-6-phosphate is the first step of glycolysis, which traps glucose inside the cell.

• The net reaction of glycolysis is:

  • $ext{glucose} + 2 ext{ADP} + 2 ext{Pi} + 2 ext{NAD}^+ → 2 ext{pyruvate} + 2 ext{NADH} + 2 ext{ATP}$

• For each glucose, the output includes: 2 pyruvates, 2 ATP, and 2 NADH.

• Alternative monosaccharides can enter glycolysis as glucose-6-phosphate or fructose-6-phosphate.

ΔG Values of Glycolysis Reactions

• Notable reactions have high negative ΔG values, indicating irreversibility:

  1. Hexokinase Reaction:

  • Catalyzed by Hexokinase, $ext{ΔG°'} = -20.9 ext{kJ/mol}, ext{ΔG} = -27.2 ext{kJ/mol}$

  1. Phosphofructokinase Reaction:

  • $ext{ΔG°'} = -17.2 ext{kJ/mol}, ext{ΔG} = -25.9 ext{kJ/mol}$

  1. Pyruvate Kinase Reaction:

  • $ext{ΔG°'} = -23.0 ext{kJ/mol}, ext{ΔG} = -13.9 ext{kJ/mol}$

• Regulation focuses on hexokinase, phosphofructokinase, and pyruvate kinase.

Fermentation Pathways

• Glycolysis does not consume oxygen, allowing ATP production under anaerobic conditions.

• NAD+ is consumed and must be regenerated to sustain glycolysis.

Pyruvate Reduction

• Two main fermentation pathways exist to regenerate NAD+:

  • Lactate fermentation:

  • $ext{pyruvate} + ext{NADH} → ext{lactate} + ext{NAD}^+$

  • Net reaction: $ext{glucose} + 2 ext{ADP} + 2 ext{Pi} → 2 ext{lactate} + 2 ext{ATP}$

  • Ethanol fermentation:

  • Two-step reaction to produce alcohol:

    1. $ext{pyruvate} + ext{H}^+ → ext{CO}_2 + ext{acetaldehyde}$

    2. $ext{acetaldehyde} + ext{NADH} → ext{ethanol} + ext{NAD}^+$

  • Net reaction: $ext{glucose} + 2 ext{ADP} + 2 ext{Pi} → 2 ext{ethanol} + 2 ext{CO}_2 + 2 ext{ATP}$

Gluconeogenesis

• Occurs when blood glucose is low and glycogen stores are depleted, primarily in the liver.

• Various precursors can be used, including:

  • Pyruvate, glycerol, lactate, citric acid intermediates, and amino acids.

• The net reaction for gluconeogenesis using pyruvate is:

  • $2 ext{pyruvate} + 4 ext{ATP} + 2 ext{GTP} + 2 ext{NADH} → ext{glucose} + 4 ext{ADP} + 2 ext{GDP} + 6 ext{Pi} + 2 ext{NAD}^+$

• The process requires higher energy input compared to glycolysis (4 ATP equivalents consumed).

• Liver cells can switch between gluconeogenesis and glycolysis to avoid futile cycles.

• Fructose-1,6-bisphosphatase, an enzyme in gluconeogenesis, is regulated by fructose-2,6-bisphosphate (F2,6P) and AMP.

Pentose Phosphate Pathway

• Generates NADPH through the oxidation of glucose-6-phosphate.

• Under conditions where both NADPH and ATP are needed, the net reaction is:

  • $3 ext{G6P} + 6 ext{NADP}^+ → 2 ext{fructose-6-phosphate} + ext{glyceraldehyde phosphate} + 6 ext{NADPH} + 3 ext{CO}_2$

• Produces ribose-5-phosphate for nucleotide synthesis as required.

Review Questions

1. Discuss the regulation of hexokinase and its benefits to the organism. Why is glucokinase in liver cells not inhibited by its product?

2. Compare the pyruvate/lactate ratio in anaerobic human muscle cells versus aerobic cells.

WileyPLUS Questions for Chapter 13:

• Questions 3, 11, 37, 39, 45, 47, 49, 51a, 51b, 53, 61, 67, 69b, 87