Lecture 4.1 - Energy storage - glycogen and lipids

Nutrients of Human Metabolism

• Carbohydrates, lipids, and proteins serve as fuel molecules for the human body
• Absorbed end products of carbohydrates are monosaccharides, lipids are monoacylglycerol and long-chain fatty acids, and proteins are peptides

Carbohydrates

• Contain carbon, hydrogen, and oxygen atoms
• Primary source of energy is glucose, which has different fates depending on the body's needs
• Includes sugars, fruits, vegetables, fibers, and legumes

Glucose

• Most important fuel source for life
• Preferred energy source for the nervous system during initial physical activity
• Lack of glucose in the brain can lead to neurological issues
• Essential building block found in cell membranes, with small quantities stored
• Cannot enter cells by simple diffusion, requires GLUT molecules and insulin presence
• Glucose homeostasis requires a balance between glucose diffusion, storage, and metabolism

Storage of Glucose - Glycogen

• Glucose can be stored as glycogen, a polymer of glucose
• Efficient storage with minimal osmotic effect
• Liver can supply approximately 16 hours of glucose
  • Muscle stores approximately 400g of glycogen
  • Liver stores approximately 75g of glycogen

Glycogen Synthesis - Glycogenesis

• Initiated by the anabolic hormone insulin
• Hexokinase is an important enzyme

Glycogen Degradation - Glycogenolysis

• Provides glucose during short periods of fasting, between meals, and during sleep
• Regulated by glucagon and adrenal catecholamines epinephrine and norepinephrine
• Pathway is not a reversal of the synthetic pathway

Regulation of Glycogen Metabolism

• Synthesis: insulin activates glycogen synthase
• Degradation: regulated by glycogen phosphorylase
• Allosteric control from adrenaline, insulin, and glucagon hormones

Disorders of Glycogen Metabolism

• Incidence: 1 in 20,000 to 1 in 40,000
• Arise from deficiency or dysfunction of enzymes in glycogen metabolism
• Affects liver and/or muscle, leading to abnormal glycogen structure and excess glycogen storage

Glycogen Metabolism in Clinical Context

• Von Gierke disease: deficiency of glucose 6-phosphate enzyme, leading to accumulation of glucose-6-phosphate intracellularly
  • 1 in 100,000 births, inherited as autosomal recessive traits
  • Signs and symptoms: hypoglycemia, lactic acidosis, enlarged liver, and cerebral damage

Glycolysis

• Enzymatic catabolism of glucose into two pyruvate molecules and 2 ATPs
• Anaerobic metabolism of glucose, important during initial physical activity or limited oxygen availability
• Ten-step reaction, with rate-limiting enzyme phosphofructokinase
• Energy-requiring phase: two ATPs spent
• Energy-releasing phase: four ATPs produced

Gluconeogenesis

• Synthesis of new glucose from non-carbohydrate substrates such as lactate, pyruvate, glycerol, and alanine
• Occurs in the liver and kidney cortex
• Response to stress situations (e.g., fasting, starvation, prolonged exercise) under hormonal control

Lipid Storage

• Fatty acids stored primarily in adipocytes as triacylglycerol
• Triacylglycerol must be hydrolyzed to release fatty acids
• Triacylglycerols are highly calorific and efficient in producing energy
• Hormonal control:
  • Insulin promotes storage
  • Glucagon, adrenaline, cortisol, and GH promote mobilization

Lipolysis - Mobilization of Fatty Acids

• Adipocytes release triacylglycerol, which is broken down into glycerol and non-esterified fatty acids
• Regulation:
  • Insulin inhibits HSL
  • Epinephrine, norepinephrine, ACTH, and glucagon activate HSL

Fatty Acid Oxidation

• Beta-oxidation source of energy during periods of fasting and exercise
• Supply energy when glycogen and gluconeogenic precursors become scarce
• FA activates as FA-CoA derivative
• Occurs in the mitochondria
• 4 ATP per round - beta-oxidation is very efficient

Lipogenesis - Fatty Acid Synthesis

• Fatty acids synthesized from acetyl-CoA
• Requires ATP and NADPH
• Occurs in the cytoplasm of liver cells
• Acetyl-CoA comes from mitochondria via transport mechanism across mitochondrial membrane

Fatty Acid Synthesis/Lipid Storage

• AMPK is an allosteric regulator

Lipogenesis vs Lipolysis

• Opposite processes, with lipogenesis promoting fatty acid synthesis and lipolysis promoting fatty acid mobilization