Nutrition & Metabolism Flashcards
What is metabolism?
Metabolism is the chemical reactions in living organisms that maintain life.
What is intermediary (or fuel) metabolism?
intermediary (or fuel) metabolism is the reactions involving the degradation, synthesis and transformation of the energy rich organic molecules - protein, carbohydrate and fats.
What is anabolism and catabolism?
Anabolism is the synthesis of larger macromolecules.
Catabolism is their degradation (hydrolysis, oxidation).
Describe the fuel metabolism activities
What are the reactions of fuel metabolism?
How is energy extracted from biomolecules?
~30 ATP molecules generated per oxidised glucose.
ATP is an important carrier of energy.
ATP -> ADP + Pi + energy
Energy stored in the high-energy phosphate bond is released when the bond is broken during the removal of the phosphate group.
- Glycolysis (within cytosol): glucose is converted by series of enzymatic reactions into 2 pyruvate molecules producing net release of energy (2 ATPs per glucose molecule). Does not require oxygen.
Glycogen glycogenolysis into glucose.
Protein proteolysis into amino acids. - Citric acid cycle (within mitochondria): acyl unit from acetyl CoA combines with oxaloacetate molecule to form citrate - further series of reactions produces ATP, NADH, and FADH2.
triglycerides (fat) lipolysis into fatty acids
*Note: if inadequate oxygen, pyruvate is not converted into acetyl CoA and does not enter the mitochondrion. Instead, pyruvate is converted to lactate and there is no further ATP production.
- Electron transport - energy from high-energy electrons of NADH and FADH2 transferred to ATP via mitochondrial enzymes. Oxygen required.
Describe the absorptive (fed) and post-absorptive (fasted) states.
- the brain must be continuously supplied with glucose (no carbohydrate storage).
- after a meal, nutrients are ingested and are entering the blood - causing high glucose levels.
- food intake is intermittent, therefore nutrients must be stored.
- in post-absorptive (fasted) state, stored substrates are degraded to release utilisable units (glucose, fatty acids, amino acids, etc.)
Fuel metabolism regulation via insulin and glucagon
Absorptive state:
insulin > glucagon
increased glucose oxidation, glycogen synthesis, fat synthesis, and protein synthesis.
Post-absorptive state:
glucagon > insulin
Adrenaline Glucocorticoids (cortisol) growth hormone
Increased glycogenolysis, glucoeogenesis, ketogenesis, protein breakdown (longer term).
Describe the regulation of insulin secretion.
Inhibitors:
1. low plasma glucose
2. sympathetic stimulation (inc. adrenaline from adrenal glands).
3. low free fatty acids
4. somatostatin.
Stimulators:
1. high plasma glucose
2. GI hormones (e.g., GLP-1, GIP)
3. high free amino acids
4. parasympathetic stimulation.
The endocrine pancreas
exocrine pancreas - comprised of acini - secrete digestive enzymes and bicarbonate into duodenum
endocrine pancreas - comprised of islets of langerhans (<2% of the total cellular mass) - secrete insulin and glucagon into blood.
How does insulin promote glucose entry into skeletal and adipose cells?
- No Insulin Scenario:
Glucose outside cell
Insulin receptor inactive
GLUT-4 transport protein in secretory vesicle
No glucose entry - Insulin Present Scenario:
Insulin binds to receptor
Signal transduction cascade
Exocytosis of GLUT-4
Glucose enters the cell
Describe the roles of glucose transporters (GLUTs).
Not regulated by insulin:
GLUT-1: facilitates the transport of glucose across the plasma membranes of cells, e.g. across blood brain barrier.
GLUT-2: principal transporter for transfer of glucose between liver and blood, and for renal glucose reabsorption.
GLUT-3: main transporter of glucose into neurons.
Regulated by Insulin:
GLUT-4: SK muscle and adipose cells.
Describe how Insulin increases metabolic use of glucose.
- Insulin binds to receptor.
- Activates IRS and 2nd messenger pathways.
- Increases GLUT-4 transport activity.
- Alters enzyme activity and transcription factors.
- Leads to metabolic changes for glucose use.
Describe how liver and Skeletal Muscle cell store excess glucose as glycogen under influence of insulin
- High Insulin triggers GLUT-2 in liver cells.
- Glucose enters cells (from high to low concentration).
- Activates signal cascade inside the liver cell.
- Converts glucose to glucose-6-phosphate.
- Glucose-6-phosphate is stored as glycogen.
- Lowers intracellular glucose to maintain glucose uptake.
How does hepatocytes look when they are fed enough?
Pink areas are accumulation of glycogen
What are the triggers for glucagon secretion and inhibition?
Inhibited by:
1. High plasma glucose
2. Insulin
3. Somatostatin
4. High free fatty acids and ketoacids
Stimulated by:
1. Low plasma glucose
2. Sympathetic stimulation (Catecholamines)
3. High free amino acids
Low free fatty acids
Describe the actions of glucagon.
Liver:
↓ Glycogen synthesis and ↑ Glycogenolysis (glycogen breakdown)
↑ Gluconeogenesis (production of new glucose)
↑ Ketogenesis (conversion of fatty acids to ketones)
↑ Blood ketones
Adipose Tissue:
↑ Fat breakdown (lipolysis)
↓ Triglyceride synthesis
↑ Circulating free fatty acids
Overall Effect:
Glucagon mobilizes glucose and fatty acids, ensuring energy availability during low glucose states.
Describe the Post absorptive fasted state
Low Plasma Glucose
↓ Plasma glucose triggers:
↑ Glucagon release from α-cells.
↓ Insulin release from β-cells.
Effects of Glucagon:
Stimulates the liver to:
↑ Glycogenolysis (breakdown of glycogen to glucose).
↑ Gluconeogenesis (formation of new glucose from lactate, pyruvate, and amino acids).
↑ Ketone production from fatty acids (for prolonged hypoglycemia).
Effects of Low Insulin:
Reduces glucose uptake in muscle and adipose tissue, preserving glucose for vital organs like the brain.
Outcome:
↑ Plasma glucose levels to maintain energy supply.
Ketones can be used as an alternative energy source for the brain and peripheral tissues.
