Molecular Biology - Integration of Metabolism Flashcards
AtherEnergy intake
Has to be tightly coordinated with energy expenditure ; different tissues have different environments
Muscles
Very high periods of ATP requirement and relies upon carbohydrates and fatty acid oxidation
How much of total body weight is muscle?
40%
Brain and nervous
Has a continuous ATP requirement ; cannot utilise fatty acids as a fuel source - 2% of total body weight
Adipose tissue
Long term storage site for triglycerides
Heart
1% of total body weight ; can oxidise fatty acids and carbohydrates with 10% of resting metabolic rate
Liver
2.5% of total body weight ; 20% of resting metabolic rate - main glycogen store and source of blood glucose
Brain
Requires continuous supply of glucose and brain cannot metabolise fatty acids
Ketone bodies can partially substitute for glucose
Too little glucose
Hypoglycaemia - cause faintness and coma
Too much glucose
Hyperglycaemia can cause irreversible damage
ATP requirements
Light contraction - requirement met by OxPhos
Vigorous contraction - O2 limiting factor means glycogen breakdown in muscles and lactate formation
Heart
Must beat constantly and is designed for completely aerobic metabolism and rich in mitochondria ; heart utilises free fatty acids and ketone bodies
Loss of O2
Leads to cell death and myocardial infarction ; energy demand»_space;> energy supply
Liver
Wide repertoire of metalolic processes - can interconvert nutrients ; glucose storage organ (glycogen)
Role of liver
Role in lipoprotein metabolism and transport of triglycerides/cholestrol
Excess glucose-6-phosphate
Can be used to generate glycogen in liver and muscle
Glucose 6 phosphate another fate
Via PPP makes nucleotides
Excess acetyl-CoA
Makes fatty acids and cholesterol
Fasting =
Ketone bodies
Extreme exercise
Demand outweighs supply and lactate is produced
To avoid hypoglycaemia
Breakdown liver glycogen stores
Release free fatty acids from adipose tissue
Convert acetyl CoA into ketone bodies
If all glycogen stores are used up
Gluconeogenesis
TCA Cycle
OAA+Acetyl -> citrate
5c = a-ketoglutarate
4c = succinylcholine-CoA
Succinate
Fumarate
L-Malate (cycle begins again)
Gluconeogenesis is
Pyruvate to Glucose C6
When is lactate generated?
By skeletal muscle during strenuous exercise when rate of glycolysis exceeds rate of TCA cycle and electron transport chain (anaerobic respiration)
What does lactate do?
Taken up by the liver and used to regenerate pyruvate by lactate dehydrogenase - Cori cycle
Where do amino acids come from?
Diet or during starvation from breakdown of skeletal muscle
Where does glycerol come from?
Triglyceride hydrolysis ; glycerol backbone is used to generate DHAP
Pathway - gluconeogenesis
Pyruvate -> OAA -> Phosphoenol pyruvate (3C) -> G3P (+DHAP from glycerol) -> Fructose-1,6-bisphosphate -> Fructose-6-phosphate -> Glucose-6-phosphate (which creates glycogen when in excess) -> Glucose
Gluconeogenesis
Key steps from
Pyruvate to OAA to Phosphoenolpyruvate
Fructose-1,6-bisphosphate to fructose-6-phosphate
G6P to Glucose
KEY STEPS MUST BE BYPASSED BY NON-GLYCOLYTIC PATHWAYS
What is different about glycolysis and gluconeogenesis?
Overall delta G value for a straight reversal of glycolysis is +90kJ which is energetically unfavourable - SO MUST find a way to bypass those kinase driver reactions
How to turn energetically unfavourable process into favourable one?
6 phosphoanhydride bonds are required
4 extra enzymes gluconeognesis
Pyruvate to OAA (-2atp) - pyruvate carboxylase
OAA to phosphoenolpyruvate (-2gtp) phosphoenolpyruvate carboxykinase
Fructose-1,6-bisP to fructose-6-p ; fructose-1,6-bisphosphatase
Glucose-6-p to glucose ; glucose-6-phosphatase
Delta g for gluconeogenesis
-38
Glucogenic amino acids
Used to generate glucose via glucoseneogenesis
Ketogenic amino acids
Used to synthesis fatty acids and ketone bodies
Deamination of the 20 amino acids
Gives rise to 7 amino acids
OAA
FUMARATE
SUCCINATE
SUCCINYL-COA
PYRUVATE
ACETYL-COA
A-KETOGLUTARATE
Fatty acids
CANNOT be converted into glucose via gluconeogensis but can be converted into ketone bodies to be used by muscle/brain
When muscles contract
Demand for ATP increases so more glucose transporters
Adrenaline increases rate of glycolysis in the muscle and increasing rate of gluconeogenesis in the liver/release of fatty acids from adipocytes
Anaerobic respiration
Lactate is produced by pyruvate (with H+ ion) in the muscle - passed into blood into liver and used in gluconeogenesis to synthesise more glucose
What does lactate also do?
Replenishes NAD+ levels
Michaelis constant
Concentration of substrate at which an enzyme functions at a half -maximal rate
Control of metabolic pathways - muscle
Hk I is active at very low concentrations of glucose and very sensitive to G6P inhibition
What does this mean in muscle?
Anaerobic conditions when rate of TCA drops and glycolysis slows ; hk1 is inhibited by accumulating levels of g6p
Liver HK (iV)
has a much higher km so much lower glucose affinity and less sensitive to G6P inhibition
gLUCOSE-6-PHOSPHATASE
Found in liver catalyses reverse reaction found in gluconeogenesis
Glucocorticoids
Increase synthesis of metabolic enzymes concerned with glucose availability
When fed
More glucose - more insulin - less glucagon
Glycolysis in liver produces acetyl coA which is broken down for fat synthesis
Also glycogen synthesis in muscle and liver
Overall stimulation of anabolic pathways
Fasting states
Gluconeogenesis
glycogen breakdown
glucagon release
fatty acid breakdown for tap production (preserves glucose for brain)
adrenalin stimulates glycogen breakdown and glycolysis and lipolysis (adipose)
Prolonged fasting
Adipose tissue hydrolyses triglyceride to provide fatty acids
TCA cycle intermediates reduced in amount to provide substrates for gluconeogenesis
pROTEIN BREAKDOWN provides amino acid substrates for gluconeogenesis
Ketone bodies produced from fatty acids/amino acids in liver to partially sub brain’s glucose requirement
Type 1
failure to secrete enough insulin
type 2
failure to respond appropriately to insulin
4 complications of diabetes
Hypo/hyperglycaemia
cardiovascular complications
ketoacidosis
Atherosclerosis
Buildup of fatty acids/cholestrol
