Metabolic changes in health and disease Flashcards
What percentage of glucose absorbed after a meal travels to the liver?
95+%
What happens to the glucose after it has traveled to the liver (in percentages)?
- ~35% metabolised in the liver
* ~65% continues on, to be distributed to other tissues
What are the two states of metabolism?
1) Fed (absorptive) state
2) Fasted (postabsorptive) state
Describe fed state metabolism
- Anabolic
- Shortly after a meal when new nutrients are available
- Nutrient molecules are used to provide energy stores of to provide the needs of growth and maintenance of cells and tissues
- Some needed immediately to provide energy
- Insulin
Describe fasted state metabolism
- Catabolic
- Body calls on the energy stores so they become depleted
- Glucagon
What determines the rate of reactions in metabolism?
- Concentrations of substrates and products of reactions
* Relevant enzymes
What are the key hormones in regulating metabolism?
- Insulin
- Glucagon
- Adrenaline and noradrenaline
What action do the hormones involved in metabolism have on their receptors?
- Activates the intracellular protein kinases
- Causes the phosphorylation of key regulatory proteins on tyrosine, serine or threonine
- The covalent modifications alter enzyme activities
What is the main function of the pancreas?
- Exocrine function (digestive enzymes
* Endocrine cells only make up 2%
How does insulin drive the fed state of metabolism?
- Stimulates glycogen synthesis in the liver and in muscle
- Stimulates the uptake of glucose into muscle and adipose tissue
- Stimulates glycolysis and hence fatty acid synthesis in the liver
- Stimulates the formation of triglycerides in fat tissue
- Stimulates protein synthesis in muscle
What is the effect of glucagon on its main target tissue?
• Main target is the liver
- Stimulates release of glucose from glycogen
- Stimulates gluconeogenesis but inhibits glucose incorporation into glycogen
What determines whether metabolism is in the fed or fasting state?
The balance between the circulating levels of insulin and glucagon
When are noradrenaline and adrenaline secreted and by what?
- Adrenal medulla - adrenaline
- Neurones of the sympathetic NS - noradrenaline
- When blood glucose falls
What is the action of adrenaline and noradrenaline regarding metabolism?
- Drives breakdown of glycogen and triglycerides
- Glycogenolytic action is mainly on muscle (producing glucose 6-P) rather than acting on the liver
- Lower glucose uptake by muscle so fatty acids are released by adipose tissue are used as fuel
- Increase glucagon secretion
- Inhibits insulin secretion
What is a normal blood glucose range?
- 80mg/100ml before a meal
- 120mg/100ml after a meal
- 4-8mmol/litre
Hypoglycaemia
- Lowered blood glucose: <3mmol/litre
* Lightheaded
Hyperglycaemia
- Elevated blood glucose: >11mmol/litre
- Excretion of glucose in the urine
- Start to feel dehydrated
Why is the liver key to regulating blood glucose levels?
Because it can take up and release large amounts of glucose (insulin and glucagon)
How long are fuel stores sufficient for?
1-3 months (depends on physical activity)
Describe the first days of starvation
- Carbohydrate stores last ~1 day
- Blood glucose falls
- Metabolism adjusts to maintain glucose at an adequate level for the brain
- Triglycerides have a limited availability to be converted into glucose
- Proteins are broken down for the production of glucose in gluconeogenesis but they also need to be preserved
- Muscle uses fatty acids from adipose tissue
- Liver: metabolises fats from adipose tissue: pyruvate, lactate and alanine are used from muscle to make glucose
Describe after around 3 days of fasting
- Ketone bodies begin to be formed from the liver
- Brain uses ketone bodies to meet requirements
- As time goes on the ability of the brain to use ketone bodies increases
- The need for amino acids for gluconeogenesis for glucose decreases which reduces the rate that muscle is broken down
How is type 2 diabetes managed?
- Exercise
* Losing weight
What is type 1 diabetes?
- Insulin dependent
- Juvenile onset
- Usually an autoimmune condition in which beta cells of the pancreas are destroyed
- Results in little insulin being released
- 10% cases
- Managed by injecting insulin
In diabetes, what is the metabolism similar to?
To that seen in prolonged fasting
Describe the body processes in diabetes
- Glycolysis is slowed
- Gluconeogenesis is stimulated using amino acids from protein breakdown
- Fatty acids (from adipose tissue) are broken down and used to form ketone bodies
- Newly formed glucose and ketone bodies pass into the blood
Why is untreated diabetes associated with excessive urination?
- Glucose leaves the blood and passes into the urine in the glomeruli of the kidney
- Normally transporters in the proximal convulsed tubule reabsorb the glucose and return it to the blood
- In diabetes the blood glucose is so high that the amount transported into the urine is too high to all be removed by the transporters
- This adds to the osmotic strength of the urine
- Harder for kidney to reabsorb water
- Urine volume greatly increased
(7. In severe cases, acidic ketone bodies also appear in the urine (ketoacidosis) adding to the osmotic strength
What are the effects of long term high blood glucose?
Damage to tissues:
• Blood vessels (polyneuropathy)
• Eyes (retinal blood vessels)
• Kidneys (urine infection; scarring and swelling in the glomeruli leading to the appearance of protein in the urine)
• Cardiovascular disease (largely a result of narrowing of the blood vessels)
- Ketone bodies can cause acidosis which can’t be completely counteracted
- Can enter coma due to low blood pH couple with dehydration
