Glucose_metabolism_MPAL_Lecture_1_2024

Glucose Metabolism: An Introduction

Metabolic Homeostasis

• Definition: The process of maintaining optimal metabolite concentrations and managing chemical energy reserves in tissues.

• Catabolism: Degradative phase of metabolism that releases energy.

• Anabolism (Biosynthesis): Building phase that requires energy.

• Integration of metabolic pathways across different pathways and organs.

The Importance of Glucose

• Chemical Composition: C6 H12 O6

• Daily consumption: Approximately 200g of glucose, with 80% used by the brain and red blood cells.

• Maximum blood glucose content: 10g; replenished through dietary carbohydrates, glycogen breakdown, and gluconeogenesis.

• Regulation: Blood glucose levels must remain between 3mM to 8mM, ideally around 4.5mM (70−100 mg/100mL), with some fluctuation after meals.

Vulnerability of the Brain

• The brain is particularly vulnerable to low glucose (hypoglycemia) as it relies on aerobic metabolism of glucose for energy and cannot store significant amounts of glucose.

• Brain cells cannot metabolize substances other than glucose or ketones, nor can they extract sufficient glucose from low extracellular concentrations.

Key Areas of Focus

• Understanding glucose: its significance and chemistry.

• Regulation of glucose levels through hormones (Insulin) and its relation to diabetes.

Glucose Metabolism Overview

• Energy Production: Glycolysis and TCA cycle produce ATP.

• Storage: Glycogen is formed through glycosidic linkages.

Structure and Chemistry of Glucose

• Chemical Characteristics: Glucose has an aldehyde group and five OH groups, making it very polar.

• Cyclic Form: Glucose primarily exists in a pyranose form.

• Hemi-acetal Formation: Glucose can form hemi-acetals that are crucial in its metabolism.

Glucose Numbering System

• Carbon Atom Numbering: Carbon atoms are numbered 1 through 6, from the aldehyde carbon.

Glucose Storage and Glycosidic Linkage

• Poly-saccharide Formation: Glucose forms disaccharides and polysaccharides through α 1-4 glycosidic linkages.

• Activation for Glycosidic Linkage: Formation is not spontaneous and requires specific conditions for the OH-group at the hemi-acetal to be activated.

Glycogen Synthesis and Structure

• Synthesized by: The enzyme glycogen synthase.

• Structure involves nonreducing ends, which are vital for glucose storage.

Dangers of High Glucose Concentrations

• Diabetes Mellitus: A group of disorders characterized by prolonged high blood glucose concentrations.

• Causes include insufficient insulin production or inadequate response to insulin.

Glycation Consequences

• Protein Glycation: High glucose levels lead to non-enzymatic modification of proteins, including hemoglobin.

• Schiff Base Formation: Reaction with amino groups in proteins forms imines and leads to various complications in diabetes.

Hemoglobin Glycation

• An important indicator of diabetes, measured via HbA1c levels, reflecting glucose concentration over time.

• Techniques involve detecting glycated hemoglobin through electrophoretic separation.

Glucose Uptake and Storage

• Importance: Glucose uptake and storage is crucial for energy metabolism.

• Transport Mechanisms: Glucose is transported into cells via glucose transporters.

• Types of glucose transporters play different roles in maintaining glucose levels.

Basic Glucose Cycle

• Cycle Overview: Involves storage sources: diet, glycogen, and gluconeogenesis, leading to ATP production.

Regulation of Glucose Levels in Mammals

• Pancreatic Hormones: Low blood glucose stimulates glucagon release, while high blood glucose triggers insulin release.

• Homeostasis: The liver releases glucose into the blood, and fat cells take glucose from the blood to maintain normal levels.

Glucose Uptake Mechanisms

• Membrane Role: Membrane integrity is key for glucose transport via various transporter families (SGLT for active transport and GLUT for facilitated transport).