MCAT Biochemistry: Carbohydrate Metabolism I

Lecture Overview

• Lecturer: Iman
• Topic: Carbohydrate Metabolism Part 1
• Key Concepts Covered: Glycolysis, Galactose/Fructose Metabolism, Pyruvate Dehydrogenase, Glycogenesis, Glycogenolysis, Gluconeogenesis, Pentose Phosphate Pathway (PPP).

Importance of Blood Glucose

• Constant blood glucose concentration critical: ~100 mg/dL (5.6 mM).
• High glucose -> Damage: retina, kidneys, blood vessels, nerves.
• Maintained by interplay of endocrine, digestive, neurological systems.

Glucose Transport and Cellular Respiration

Key Notes for MCAT

1. Glucose Entry into Cells: Driven by concentration, independent of sodium.
2. Glucose Transporters: GLUT1, GLUT2, GLUT3, GLUT4.
   • GLUT2: Liver (Storage) & Pancreas (Regulation by Insulin).
   • GLUT4: Adipose Tissue & Muscle (Stimulated by Insulin).

Cellular Respiration Overview

• Composed of Glycolysis, Citric Acid Cycle, Oxidative Phosphorylation.
• Glycolysis: Focus of this chapter.
• Citric Acid Cycle & Oxidative Phosphorylation: Discussed in Part 2.

Glycolysis

Process of Glycolysis

• Location: Cytosol.
• Starting Material: 1 Glucose (6-carbon).
• End Product: 2 Pyruvates (3-carbons each).

Phases of Glycolysis

1. Energy Investment Phase: ATP used.
2. Energy Payoff Phase: ATP and NADH produced.

Detailed Steps

1. Hexokinase: Glucose -> Glucose-6-phosphate (uses 1 ATP).
2. Phosphohexose Isomerase: Glucose-6-phosphate -> Fructose-6-phosphate.
3. Phosphofructokinase: Fructose-6-phosphate -> Fructose-1,6-bisphosphate (uses 1 ATP).
4. Aldolase: Fructose-1,6-bisphosphate -> 2 three-carbon molecules (G3P & DHAP).
5. G3P Dehydrogenase: G3P -> 1,3-bisphosphoglycerate (produces NADH).
6. Phosphoglycerate Kinase & Pyruvate Kinase: Form ATP (substrate-level phosphorylation).
   • Net Yield: 2 ATP (from 4 produced - 2 invested), 2 NADH.
   • Pathway's Flexibility: Occurs with or without oxygen.

Galactose and Fructose Metabolism

Galactose Metabolism

• Source: Lactose from milk.
• Enzymes: Galactokinase, Galactose-1-phosphate uridyltransferase, Epimerase.
• Product: Glucose-1-phosphate.

Fructose Metabolism

• Source: Honey, fruit, sucrose.
• Enzymes: Fructokinase, Aldolase B.
• Products: Glyceraldehyde, DHAP.

Pyruvate Dehydrogenase

• Conversion: Pyruvate -> Acetyl-CoA
• Role: Initiates Citric Acid Cycle (if ATP needed) or fatty acid synthesis (sufficient ATP).
• Regulation: Stimulated by Insulin, Inhibited by Acetyl-CoA.

Glycogenesis and Glycogenolysis

Glycogenesis

• Synthesis of Glycogen from Glucose.
• Key Enzymes: Glycogen synthase (alpha-1,4 linkage), Branching enzyme.
• Regulation: Promoted by Insulin, inhibited by Glycogen Phosphorylase.

Glycogenolysis

• Breakdown of Glycogen to Glucose.
• Key Enzymes: Glycogen Phosphorylase (alpha-1,4 cleavage), Debranching enzyme.
• Regulation: Promoted by Glucagon, inhibited by Insulin.

Gluconeogenesis

• Production of Glucose from Non-Carbohydrate Precursors: Amino acids, lactate, glycerol.
• Location: Cytoplasm and Mitochondria (mainly liver).
• Key Steps and Enzymes:
  • Pyruvate -> Oxaloacetate (Pyruvate carboxylase).
  • Oxaloacetate -> PEP (PEPCK).
  • Rate-limiting step: Fructose-1,6-bisphosphatase (fructose-1,6-bisphosphate -> fructose-6-phosphate).
  • Regulation: Inhibited by Insulin, activated by Glucagon.

Pentose Phosphate Pathway (PPP)

Functions

1. NADPH Production.
2. Ribose-5-phosphate Production for Nucleotide Synthesis.

Phases and Regulatory Enzymes

• Oxidative Phase Begins: Glucose-6-phosphate -> Ribose-5-phosphate (produces NADPH).
• Key Enzyme: Glucose-6-phosphate dehydrogenase (G6PD).
• Regulation:
  • Induced by Insulin.
  • Inhibited by NADPH.
  • Activated by NADP+.

Summary

• Important MCAT Enzymes to Know:
  • Glycolysis: Phosphofructokinase-1 (PFK-1).
  • Fermentation: Lactate Dehydrogenase.
  • Glycogenesis: Glycogen Synthase.
  • Glycogenolysis: Glycogen Phosphorylase.
  • Gluconeogenesis: Fructose-1,6-bisphosphatase.
  • PPP: Glucose-6-phosphate Dehydrogenase.