Metabolism and Glycolysis Overview

The Central Role of Glucose in Metabolism

• Glucose is the primary energy source for most cells in the body.
• It plays a central role in metabolic pathways.
• The breakdown of glucose is essential for ATP (energy) production.

Glycolysis

• Glycolysis is the first stage of glucose metabolism.
• It occurs in the cytoplasm of cells.
• It is a 10-step process that breaks down glucose into pyruvate.
• There are three irreversible steps that are regulated:
  • Phosphorylation of glucose
  • Phosphorylation of fructose-6-phosphate
  • Transfer of a phosphate group from PEP to ATP to produce pyruvate
• Two types of glycolysis:
  • Aerobic glycolysis: This happens in the presence of oxygen and results in pyruvate.
  • Anaerobic glycolysis: Lack of oxygen results in lactate production.
• Net synthesis: 2 ATP molecules

Gluconeogenesis, Glycogenolysis, and Glycogenesis

• Gluconeogenesis: Synthesis of glucose from non-carbohydrate sources (e.g. pyruvate, lactate, glycerol, and amino acids).
• Glycogenolysis: Breakdown of glycogen into glucose.
• Glycogenesis: Synthesis of glycogen from glucose.

Hexose Monophosphate Pathway (HMP)

• Also known as the pentose phosphate pathway (PPP) or phosphogluconate pathway.
• Occurs in the cytosol.
• It is an alternative pathway for glucose metabolism.
• Produces:
  • Reducing equivalents (NADPH) for reductive biosynthesis
  • Ribose-5-phosphate for nucleotide synthesis
• No net energy production or consumption.
• Two main phases:
  • Oxidative phase: generates NADPH and produces ribulose-5-phosphate
  • Non-oxidative phase: Interconverts sugars with different carbon lengths using multiple enzymes.

Metabolism of Other Carbohydrates (fructose, galactose)

• Fructose:
  • Phosphorylated to fructose-6-phosphate by hexokinase.
  • Can enter the glycolytic pathway at the second step.
• Galactose:
  • Needs to be converted to glucose-1-phosphate before entering glycolysis.
  • Galactose is phosphorylated to galactose-1-phosphate by galactokinase.
  • Galactose-1-phosphate is then converted to glucose-1-phosphate by galactose-1-phosphate uridyltransferase (GALT).

Ketone Body Metabolism

• Ketone bodies are produced when there’s an excess of glycerol and fatty acids compared to carbohydrates and proteins.
• They are synthesized from acetyl-CoA.
• They become a major energy source particularly in type I diabetic individuals who lack insulin.
• They are oxidized to produce ATP and H+, making the cellular environment acidic.
• Excessive ketone bodies lead to diabetic ketoacidosis.

Glycogen Metabolism Overview

• Glycogen is the primary storage form of glucose in animals.
• In the liver, glucose-6-phosphate can be converted to glucose and released into the bloodstream.
• Glycogenesis (glycogen synthesis):
  • Occurs when there’s an excess of glucose.
  • Glucose is converted to glucose-6-phosphate and then glucose-1-phosphate.
  • UDP-glucose is the precursor for glycogen synthesis.
  • Catalyzed by glycogen synthase and branching enzyme.
• Glycogenolysis (glycogen breakdown):
  • Occurs when glucose levels are low.
  • Catalyzed by glycogen phosphorylase and debranching enzyme.
  • Glucose-1-phosphate is then converted to glucose-6-phosphate.

Glycogenesis: Step-by-Step Breakdown

• Step 1: Phosphorylation:
  • Glucose enters the cells via GLUT transporters (GLUT2 in hepatocytes and GLUT4 in myocytes and adipocytes).
  • It is phosphorylated to glucose-6-phosphate by hexokinase (muscle) or glucokinase (liver).
• Step 2: Isomerization:
  • Glucose-6-phosphate is converted to glucose-1-phosphate by phosphoglucomutase.
• Step 3: UDP-Glucose formation:
  • Glucose-1-phosphate and UTP react to form UDP-glucose and pyrophosphate.
  • Catalyzed by UDPG pyrophosphorylase.
  • Hydrolysis of pyrophosphate by pyrophosphatase favors the forward reaction.
• Step 4: Chain initiation:
  • Glycogenin acts as a primer for initial glucose attachment.
  • UDP-glucose attaches to the tyrosine residue of glycogenin.
• Step 5: Chain Extension:
  • Glycogen synthase catalyzes the formation of glycosidic bonds between UDP-glucose and the terminal glucose of glycogen.
  • UDP is released.
  • Glucose is added to the non-reducing end of the glycogen chain.
• Step 6: Branching:
  • Branching enzyme transfers glucose residues from the non-reducing end of the chain, forming alpha-1,6 glycosidic bonds.
  • This creates branches in the glycogen molecule.

Key Enzymes in Glycogen Metabolism

• Glycogen synthase: Catalyzes glycogen synthesis.
• Branching enzyme: Creates branches in the glycogen molecule.
• Glycogen phosphorylase: Catalyzes glycogen breakdown.
• Debranching enzyme: Removes branches from the glycogen molecule.
• Hexokinase/Glucokinase: Phosphorylates glucose.
• Phosphoglucomutase: Converts glucose-6-phosphate to glucose-1-phosphate.
• UDPG pyrophosphorylase: Catalyzes the formation of UDP-glucose.

This quiz explores the central role of glucose in metabolism, including glycolysis, gluconeogenesis, glycogenolysis, and glycogenesis. Test your knowledge on the processes involved in energy production and how glucose serves as a key metabolic intermediate.