Integration of Metabolism Flashcards
How much of the total body weight is muscle?
40%
How much of the total body weight is brain and nervous tissue?
2%
How much of the total body weight is adipose tissue?
15%
How much of the total body weight is the heart?
1%
How much of the total body weight is the liver?
2.5%
What is muscle ATP requirement like?
High during vigorous contraction
What is brain and nervous tissue ATP requirement like?
Continuously high —> 20% BMR
What is the heart’s ATP requirement like?
Constant —> 10% BMR
What is the liver’s ATP requirement like?
Constantly high —> 20% BMR
Which 2 energy sources do skeletal muscle and the heart rely on?
- Carbohydrates
- Fatty acid oxidation
Which energy source does the brain and nervous tissue rely on?
- Glucose (needs continuous supply)
- Ketone bodies can partially substitute
Why can’t the brain metabolise fatty acids?
Can’t cross blood-brain barrier
How does hypoglycaemia and hyperglycaemia affect the brain?
- Hypoglycaemia —> faintness/coma
- Hyperglycaemia —> irreversible damage
What is the source of energy for muscles during light vs vigorous contraction?
- Light —> oxidative phosphorylation
- Vigorous —> glycogen breakdown and lactate formation (supplies NAD+ for glycolysis)
What type of metabolism is the heart dependant on?
Aerobic
What happens to the heart when O2 is limited or energy demand > supply?
Cell death —> myocardial infarction
What are the 3 important functions of the liver for metabolism?
- Interconverts nutrient types
- Stores glycogen
- Lipoprotein metabolism (for triglyceride and cholesterol tranport)
What should blood glucose levels be maintained at?
4.0-5.5 mM
How does the body prevent hypoglycaemia? (3)
- Glycogenolysis
- Release free fatty acids from adipose tissue
- Ketone body production from acetyl CoA by the liver
Which 3 molecules are important for gluconeogenesis?
- Lactate —> regenerate pyruvate via LDH
- Amino acids —> converted to TCA substrates
- Glycerol of triglycerides —> generates DHAP
What is the ΔG of gluconeogenesis?
-38 kJ/mol
Which bonds are needed to make gluconeogenesis energetically favourable and how many are needed?
6 Phosphoanhydride bonds
What are the 6 steps of gluconeogenesis?
- Pyruvate —> oxaloacetate
- Pyruvate carboxylase - —> PEP
- PEP carboxykinase - —> F16BP
- —> F6P
- F16BPase - —> G6P
- —> Glucose
- G6Pase
How many ATPs are used in gluconeogenesis?
6
Which gluconeogenesis reactions use ATP?
- Pyruvate —> oxaloacetate -2 ATP
- Oxaloacetate —> PEP -2 GTP
- PEP —> F16BP -2 ATP
What are glucogenic amino acids?
Can generate glucose via gluconeogenesis
What are ketogenic amino acids?
Can generate ketone bodies and fatty acids (via generating acetyl CoA)
What 2 things does contracting muscle require?
- inc ATP
- inc Glucose transporters
Why is adrenalin secreted during increased muscle contraction?
- Increases gluconeogenesis in liver
- Increases fatty acid release from adipocytes
How is lactate involved in sourcing ATP when there is high demand? (2)
- Lactate synthesis regenerates NAD+ for glycolysis
- Lactate used in gluconeogenesis
What is The Michaelis Constant?
Concentration of of substrate at which enzyme functions at half Vmax
What is Km?
The Michaelis Constant
(concentration of of substrate at which enzyme functions at half Vmax)
What is Vmax?
The maximum rate of an enzymatic reaction under saturated substrate conditions
Which hexokinase is used in muscle?
I
Which hexokinase is used in the liver?
IV
What is the difference between hexokinase activity in muscles vs the liver?
- Muscle HK I low —> control glucose metabolism
- Liver HK IV high —> high G6P to G
What is the difference between the Km of muscles vs the liver?
- Muscle —> 0.1 mM
- Liver —> 4 mM
∴ More substrate needed to reach Vmax for HK IV
What is the difference between G-6-P inhibition sensitivity in muscles vs the liver?
- Muscle —> high
- Liver —> lower
When is insulin secreted and why?
When glucose levels rise
- Stimulates glucose uptake
- Stimulates glycogen and fat storage
When is glycogen secreted and why?
When glucose levels fall
- Stimulates gluconeogenesis
- Stimulates glycogen and fat breakdown
Which 3 processes is adrenalin important for in metabolism?
- Glycogenolysis (liver)
- Glycolysis (skeletal muscle)
- Lipolysis (adipose tissue)
Why are glucocorticosteroids important for metabolism?
Increase synthesis of metabolic enzymes controlling glucose availability
How are blood glucose levels controlled when blood glucose is low? (not consuming glucose)
- Glucagon secretion inc
- Insulin secretion dec
Which 4 metabolites are used during prolonged fasting and how?
- Fatty acids - released by hydrolysis of triglycerides stored in adipose tissue
- Amino acids - provide substrates for gluconeogenesis
- Ketone bodies - can partially substitute brain’s glucose requirements
- TCA intermediates - for gluconeogenesis
What is Type 1 diabetes?
Failure to secrete sufficient insulin (B-cell dysfunction)
What is Type 2 diabetes?
Failure to respond appropriately to insulin (insulin resistance)
What are the 4 complications of diabetes?
- Hypoglycaemia
- Hyperglycaemia
- Cardiovascular issues
- Ketoacidosis
