Integration Of Metabolism Flashcards
Muscle
Relies upon carbohydrate and fatty acid oxidation
Have periods of very high ATP requirement
Brain and nervous system
Cannot utilise fatty acids as a fuel source
Uses 20% of resting metabolic rate —> has continuous high ATP requirement
Adipose tissue
Long term storage site for triglycerides
Heart
Can oxidise fatty acids and carbohydrates
10% of resting metabolic rate
Liver
Main carbohydrate store
Source of blood glucose
20% resting metabolic rate
Source of ketone bodies (from fatty acids)
What does the brain require a continuous supply of?
Glucose
(Ketone bodies can partially substitute for glucose)
What can the brain not metabolise?
Fatty acids
In the brain what does too little and too much glucose cause?
Too little = hypoglycaemia —> fairness and coma
Too much = hyperglycaemia —> irreversible damage
In the muscle how are requirements met during light contraction?
OxPhos
—> O2 and blood borne glucose and fatty acids used as fuel
In the muscles how are requirements met during vigorous contraction?
Glycogen breakdown
Lactate formation
When ATP consumption > than ATP supply rate by OxPhos
—> O2 becomes a limiting factor
Metabolic features of the heart
Completely aerobic metabolism —> rich in mitochondria
Utilises TCA substrates —> free fatty acids, ketone bodies e.g.
Loss of O2 —> cell death —> myocardial infarction
What happens during extreme exercise?
ATP demand > ATP production
—> lactate produced
What happens during fasting?
Instead of entering TCA cycle —> acetyl CoA results in ketone body production
What happens if glucose levels fall below 3 mM?
Body enters a hypoglycaemic coma
How is hypoglycaemia avoided?
Breakdown of liver glycogen stores —> maintain plasma glucose levels
Release free fatty acids from adipose tissue
Convert acetyl CoA into ketone bodies via the liver
What reaction can directly enter pathway to increase oxaloacetate for gluconeogenisis?
Transamination of amino acids
—> carbon skeleton enters the cycle
Why must some redactions on gluconeogenisis be bypassed?
The forward reactions are essentially irreversible under cellular conditions
Why can’t the muscle produce glucose via gluconeogenisis?
It doesn’t have the enzyme (glucose-6-phosphatase) to bypass the reaction
Why is it important that the muscle doesn’t have glucose-6-phosphatase?
It ill reverse the reaction —> set up a futile cycle
What are glucogenic amino acids used for?
Generate glucose via gluconeogenisis
What are ketogenic amino acids used for?
Synthesis fatty acids and ketone bodies
Fats as a fuel source
Triglycerides —> fatty acids and glycerol
Fatty acid —> ketone bodies
Glycerol —> DHAP —> enter gluconeogenisis
Energy stores and consumption - Aerobic respiration
Contractions increase ATP demand
Contractions increase glucose transport
Muscle glycolysis increases (adrenalin)
Gluconeogenisis increases (adrenalin)
Fatty acids increase (adrenalin)
Energy stores and consumptions - Anaerobic respiration
ATP demand not matched by O22 delivery
Transport cannot keep up with the demand for glucose
Muscle glycogen breakdown increases
Lactate increases
Liver uses lactate to form glucose (recovery) —> replenishes NAD+ levels
Hormonal control of blood - what does insulin do?
Secreted by islets of pancreas when glucose levels rise
Stimulate uptake and use of glucose and storage of glycogen and fat
Suppresses glucagon release
Hormonal control of blood — what does glucagon do?
Secreted by islet of pancreas when glucose levels fall
Stimulates production of glucose by gluconeogenisis and breakdown of glycogen and fat
Hormonal control of blood - what does adrenalin do?
Strong and fast metabolic effects to mobilise glucose for ‘fight or flight’
Hormonal control of blood - what do glucocorticoids do?
Steroid hormones —> increases synthesis of metabolic enzymes concerned with g;leucose availability
Hormonal control of blood - right after a meal
Blood glucose levels rise —> controlled by increased secretion of insulin and reduced glucagon
Increased glucose uptake by liver
Increased glucose uptake and glycogen synthesis in muscle
Increased triglyceride synthesis in adipose tissue
Increased usage of metabolic intermediates
Hormonal control of blood - some time after a meal
Blood glucose levels start to fall and are controlled by:
Increased glucagon secretion + reduced insulin
Glucose production in liver from glycogen breakdown and gluconeogenisis
Fatty acid breakdown as alternative substrate for ATP production
Adrenalin stimulera glycogen breakdown, glycolysis + lipolyses
Hormonal control of blood - after prolonged fasting
Glucagon/insulin ratio increases further
Adipose tissue hydrolyses triglycerides to provide fatty acids
TCA cycle intermediates reduced in amount to provide substrates for gluconeogenisis
Protein breakdown provides amino acid substrates for gluconeogenisis
Ketone bodies produced from fatty acids and amino acids in liver
Type 1 diabetes
Failure to secret enough insulin (beta cell dysfunction)
Type 2 diabetes
Failure to respond appropriately to insulin levels (insulin resistance)
What are some complications of diabetes?
Hyper and hypoglycaemia
Cardiovascular complications
Ketoacidosis
