Integration Of Metbolism Flashcards
Where do muscles get energy from
Carbohydrates and fatty acid oxidation. Muscles can have periods of very high ATP requirement during vigorous contraction
What supplies energy during the light and vigorous contraction of muscles
Light = ATP consumption is met by oxidative phosphorylation ( O2 and blood borne glucose and fatty acids are used as a fuel)
Vigorous : ATP consumption is faster than the ATP supply by oxidative phosphorylation ( O2 and blood borne substrate diffusion is limiting) . So muscle stores of glycogen are broken down . In anaerobic conditions, pyrite is converted to lactate which can leave muscle and reach the liver via blood
Where does the brain and nervous tissue get energy from
Has a continuous high ATP requirement and it cannot metabolise fatty acids as so it uses carbohydrates and ketone bodies.
What is hypoglycaemia
Too little glucose and causes faintness and coma
What is hyperglycaemia
Too much glucose and can cause irreversible damage
Where does adipose tissue get energy from
It is the long term storage site for fatty acids in the form of triglycerides
Where does the heart get energy from
Fatty acids and carbohydrates. Constantly contracting and is designed completely for aerobic respiration and is rich in mitochondria- loss of O2 supply can lead to cell death and myocardial infarction
Where does the liver get energy from
The body’s main carbohydrate store ( glycogen) an a source of blood glucose. Also plays a key role in lipoprotein metabolism and the transport of triglycerides and cholesterol . Also undertakes many metabolic processes including glycolysis , gluconeogenesis and transamination
What does the pentose phosphate pathway do
It converts glucose -6- phosphate to be used as a source for nucleotide production in a pathway that generates the bulk of NADPH needed for anabolic pathways (e.g. cholesterol synthesis )
What is done in the short term to prevent the body entering hypoglycaemic coma in the short term
Breakdown of liver glycogen stores to maintain plasma glucose levels. Release free fatty acids from adipose tissue, convert acetyl coA into ketone bodies via liver. Both fatty acids and ketone bodies can be used by the muscle making more of the plasma glucose available for the brain .but within 12-18 hrs, all the glucose is typically exhausted and you need gluconeogenesis
What is the overall aim of gluconeogenesis
To make glucose from pyruvate
What are the non carbohydrate precursors that enter the gluconeogenesis pathway
Lactate , amino acids and glycerol
How can lactate be used in the gluconeogenesis pathways
It can be taken up by the liver and utilised go regenerate pyruvate by lactate dehydrogenase ( LDH) known as the Cori cycle
How can amino acids be used in the gluconeogenesis cycle
Can be derived from diet or during times of starvation ( e.g. from the breakdown of skeletal muscle . Used to produce pyruvate or convert pyruvate to oxaloacetate ( add a C).
You can have ketogenic amino acids ( give rise to skeletons which cannot enter gluconeogenesis but can be used to syntheses fatty acids and ketone bodies) . Also have glucogenic amino acids because skeletons can give rise to glucose via gluconeogenesis
How can triglyceride hydrolysis be used in the gluconeogenesis pathway
Triglyceride hydrolysis yields fatty acids and glycerol , the glycerol backbone is used to generate hydroxyacetome phosphate which combines with G3P to form 6C ( think about glycolysis)
What three reactions need to be bypassed in gluconeogenesis
The irreversible reactions catalysed by hexokinase, phsophofructokinase ( all the above are systolic) and pyruvate kinase( in mitochondria)
What is required to make the gluconeogenesis process energetically favourable
4 additional high energy bonds ( as you are effectively 4 ATP deficient )
What happen during aerobic exercise in terms of glucose
1) contractions increase ATP demand( actomyosin ATPase and cation balance)
2) contractions increase glucose transport
3) muscle glycolysis increases( Adrenalin)
4) gluconeogenesis increases (Adrenalin )
5) fatty acids increase( Adrenalin)
What happens in terms of glucose intake in terms of anaerobic conditions
1) ATP demand cannot be matched by O2 delivery
2) Transport cannot keep up with the demand for glucose
3) muscle glycogen breakdown increases
4) lactate increases
5) liver used lactate to form glucose
To replenish NAD+ levels and maintain glycolysis , pyruvate is taken up by the liver and converted into lactate by lactate dehydrogenase. Lactate can then be used by the liver to generate glucose by gluconeogenesis
What does insulin do
Secreted when the glucose levels rise ; it stimulates the uptake and use of glucose and storage as glycogen and fat
What does glucagon do
Glucagon is secreted when glucose levels fall: it stimulates the production of glucose by gluconeogenesis and the breakdown of glycogen and fat
What does Adrenalin/epinephrine
Adrenaline is the strong and fast metabolic effects to mobilise glucose for ‘fight or flight’
What do glucocorticoids do
They are steroid hormones which increase the synthesis of metabolic enzymes concerned with glucose availability
What are the effects of insulin
- increased glucose uptake by the liver : used for glycogen synthesis and glycolysis ( acetyl-CoA produced is used for fatty acid synthesis)
- increased glucose uptake and glycogen synthesis in muscles
- increased triglyceride synthesis in adipose tissue
- increased usage of metabolic intermediates throughout the body due to a general stimulators effect on synthesis and growth
What happens a long time after a meal to glucose levels
Blood glucose level start to fall and are controlled by
- increased glucagon secretion ( and reduced insulin ) from islets
- glucose production in liver resulting from glycogen breakdown and gluconeogenesis
- utilisation of fatty acid breakdown as alternative substrate for ATP production ( imp for preserving glucose in brain)
What does Adrenalin do a long time after a meal has been eaten
Adrenalin has similar effects on liver but also stimulates skeletal muscle towards glycogen breakdown and glycolysis, and adipose tissue towards fat lipolysis to provide other tissues with alternative substrate to glucose
What happens after prolonged fasting ( when glucose levels can no longer be covered by glycogen reserves )
Glucagon /insulin ratio increases further
Adipose tissue begins to hydrolyse triglyceride to provide fatty acids for metabolism (lipolysis)
TCA cycle intermediates are reduced in amount to provide substrate for gluconeogenesis
Protein breakdown provides amino acid substrates for gluconeogenesis ( proteolysis)
Ketone bodies are produced from fatty acids and amino acids in liver to substitute partially the brains requirement for glucose
What is Type 1 diabetes
Individuals fail to secrete enough insulin ( beta cell dysfunction)
What is Type 2 Diabetes
Individuals fail to respond appropriately to insulin levels ( insulin resistance)
Complications of diabetes
Hyperglycaemia with progressive tissue damage (e.g. retina, kidney, peripheral nerves)
Increase in plasma fatty acids and lipoprotein levels with possible cardiovascular complications
Increase in ketone bodies with risk of acidosis
Hypoglycaemia with consequent coma if insulin dosage is imperfectly controlled
What is ketoacidosis
High plasma volume of glucose will disturb the solute balance in the brain . There are also issues with renal function leading to dehydration . The levels of ketone bodies ( and fatty acids) will significantly lower the plasma pH disrupting the ion transport in the CNS leading to coma. High blood glucose drives urine production leading to dehydration - saline will help to rehydrate body
Type 1 diabetes
Little/no insulin secretion. People are absolutely dependent on injections of insulin. Although main problem is to do with insulin, the inaction of glucagon also contributes
Type 2 diabetes
Insulin insensitivity of tissues. As disease progresses, insulin secretion may become insufficient and injections of insulin may be required.
How can hypoglycaemia lead to coma
Lack of glucose metabolism in cells
How does hyperglycaemia lead to coma
Due to increased osmolarity of body fluids ( both directly and due to the diuresis caused by glucose excretion in urine)
How does excess insulin administration lead to hypoglycaemia
Plasma fatty acid and ketone body concentrations are also low , since insulin inhibits lipolysis and keto Genesis
Why may type 1 diabetics get hyperglycaemia
If they fail to inject insulin as they will have high plasma levels of ketone bodies and fatty acids. Glucagon is also in unapproved by insulin and so increased glycogenolysis, lipolysis and ketogenesis also occurs. This is quite rare in people with type 2 diabetes as they do secrete insulin which opposes glucagon
what is pyruvate kinase bypassed by in gluconeogenesis
phosphoenolpyruvate carboxylase and pyruvate carboxylase
what is phosphofructokinase bypassed by
Fructose 1,6 biphosphatase
what is hexokinase bypassed by
Glucose-6-phosphatase
