Glucose_metabolism_MPAL_Lecture_1_2024

Glucose Metabolism: An Introduction

• Presented by Dr. Mohinder Pal

Learning Objectives

• Understand the relationship between the chemical properties of glucose and its function.

• Recognize the necessity of regulating glucose concentrations and the potential toxicity of glucose.

• Comprehend the dual role of glucose as a fuel and structural component.

• Emphasize the importance of asking basic questions regarding glucose metabolism.

Metabolic Homeostasis

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

• Catabolism:

  • The degradative phase of metabolism that releases energy.

• Anabolism (Biosynthesis):

  • The building phase of metabolism that requires energy.

• Key metabolic pathways include amino acid metabolism, carbohydrate metabolism, and lipid metabolism.

• Metabolism is integrated among pathways and organs to maintain homeostasis.

Importance of Glucose

• Structure: C6H12O6

• Daily consumption of glucose: ~200g (primarily for brain and red blood cells).

• Maximum blood glucose content: 10g, necessitating constant replenishment through dietary carbohydrates, glycogen breakdown, and gluconeogenesis.

• Rigorous control of blood glucose levels (ideally ~4.5 mM or 70−100 mg/100mL), with fluctuations post-meal.

• It metabolises substrates other than glucose or ketone bodies

Vulnerability of the Brain

• The brain is particularly sensitive to hypoglycemia due to:

  • Limited storage for glucose.

  • Inability to synthesize glucose.

  • Dependence on aerobic metabolism of glucose.

• The brain cannot metabolize other substrates effectively, making it reliant on constant glucose supply.

Key Areas to Learn/Remember

• Definition and significance of glucose.

• Chemical properties of glucose.

• Regulation of blood glucose levels by hormones (Insulin, and its relationship with diabetes).

Glucose Metabolism Overview

• Energy Production: Glucose is metabolized to produce ATP through glycolysis and the TCA cycle.

• Storage: Glucose is stored as glycogen, linked by glycosidic bonds.

Structure and Chemistry of Glucose

• Glucose is an aldehyde with five hydroxyl (OH) groups, making it very polar.

• Chemical configuration exhibits hemiacetal formation in cyclic structures (pyranose).

Glycosidic Linkage

• Glycosidic linkages link glucose molecules to form disaccharides and polysaccharides.

• The formation of these linkages is non-spontaneous and requires activation of the OH group.

Glycogen Synthesis

• Enzyme: Glycogen synthase synthesizes glycogen.

• Structure includes a nonreducing end and can elongate through UDP-glucose activation.

Dangers of High Glucose Concentrations

• Diabetes Mellitus: A group of metabolic disorders characterized by prolonged high blood glucose levels due to either:

  • Insufficient insulin production by the pancreas.

  • Ineffective response to existing insulin.

Protein Glycation and Its Effects

• Glycation: High glucose concentrations can modify proteins, leading to ailments associated with diabetes.

• Glycation involves the non-enzymatic reaction between glucose and amino acids in proteins, leading to distinctive structural changes.

Hemoglobin Glycation

• An indicator of diabetes as high glucose modifies hemoglobin, creating glycated hemoglobin (HbA1c).

• Measurement of HbA1c: Techniques include electrophoretic separation and measurement of various forms to determine diabetes management.

Learning Outcomes

• Understand glucose chemistry and its linear and cyclic forms.

• Recognize that high glucose concentrations facilitate unwanted protein glycation.

Glucose Uptake and Storage

• Importance of glucose uptake and storage.

• Mechanisms of glucose transport into cells via glucose transporters.

Basic Glucose Cycle

• Storage Sources:

  • Diet ➔ Glycogen ➔ Glucose ➔ Gluconeogenesis ➔ Energy (ATP).

Controlling Glucose Levels in Mammals

• Homeostasis Mechanism:

  • Low Blood Glucose: Pancreas releases glucagon.

  • High Blood Glucose: Pancreas releases insulin, prompting liver and fat cells to manage glucose levels.

Glucose Transporters

• Importance of membrane transporters for glucose cellular uptake.

• Types of glucose transporters include:

  • Sodium-glucose active co-transporters (SGLT family)

  • Glucose Transporters (GLUT family)

• Mechanisms of transporter action and their differing roles in maintaining glucose homeostasis.