Endocrine Control Of Metabolism Flashcards
What process is at the core of energy metabolism?
→ TCA cycle
What do molecules have to be metabolized into to be fed into the TCA?
→ acetyl CoA
What are 5 circulating nutrients?
→ Glucose → Fatty acids → Amino acids → Ketone bodies → Lactate
What are 3 stored nutrients?
Glycogen
→ Triglycerides
→ Body proteins
What is the level of plasma glucose?
→ 5 mmol / L
What energy source does the brain use?
→ glucose metabolism
What can the blood glucose level not drop below?
→ < 2.5. mmol
What is the ultimate outcome of hypoglycaemia?
→ coma and death
What does chronic exposure to high glucose concentrations cause?
→ Protein damage via non-enzymatic glycation
How much of body weight is water and how much of this is ECF and ICF?
60% total
→ 40% ICF
→ 20% ECF
How much glucose does the brain and muscle use up?
→ 30 mmol per hour
300 mmol per hour during intense exercise
What are the two sources of plasma glucose?
→ Diet
→ Organs that can export glucose into the circulation
What prevents plasma glucose from surging or plummeting?
→hormones regulate the integration of fat, carbs and protein metabolism
→ maintain constant blood plasma glucose
What are the 2 phases of metabolism?
→ Absorptive and fasting
What does insulin promote?
→ Storage
→ Decreases plasma glucose
What are the counter regulatory hormones to insulin?
Glucagon
→ Adrenaline
→ Cortisol + growth hormone
What does insulin stimulate?
→ Uptake of glucose by skeletal muscle, adipose and other tissues
→ Glycogen synthesis in liver and skeletal muscle
→ uptake of fatty acids and amino acids
What does glucose inhibit?
→ release of glucose from the liver
→ fat and protein breakdown
What is the main effect of glucagon?
→ stimulates hepatic glucose production
What are the main effects of adrenaline?
→ Stimulates hepatic glucose production
→ Stimulates lipolysis - release of FA from adipose tissues
What are the main effects of cortisol?
→ Stimulates hepatic glucose production
→ Stimulates proteolysis - release of amino acid from body proteins
What is glycogenesis?
→ synthesis of glycogen from glucose
What are the main effects of growth hormone?
→ Stimulates hepatic glucose production
→ lipolysis
What is lipogenesis?
→ synthesis of FA from acetyl CoA
What is triglyceride synthesis?
→ Esterification of FA for storage as TG
What are the three metabolic pathways serving energy storage?
→ Glycogenesis
→ Lipogenesis
→ Triglyceride synthesis
What are the 5 metabolic pathways serving energy release?
→ Glycogenolysis → Gluconeogenesis → Lipolysis → Beta oxidation → Keto genesis
What is ketogenesis?
→ Production of ketone bodies from acetyl CoA
Why are ketone bodies useful to the brain?
→ They serve as a partial substitute for glucose
→ The brain can metabolize ketone bodies
What happens in the pancreas if the plasma glucose concentration decreases?
→ Drop is sensed by secretory cells in pancreas
→ decrease insulin secretion
→ Increase glucagon secretion
Where is hypoglycaemia sensed and what is done?
→ Sensed in brainstem → Sympathetic response → Stimulation of adrenal glands → Release adrenaline → direct stimulation of pancreas → Direct stimulation of the liver to produce glucose
What are 3 short term defences against hypoglycaemia?
→ Glucagon
→ Adrenaline
→ Sympathetic NS
What is a medium term defense against hypoglycaemia and how ?
→ Ketogenesis - fat reserves provide a partial substitute for glucose
→ Spares muscle tissue from destruction
What is a long term defense against hypoglycaemia and how ?
→ Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis
What is a defence against hyperglycaemia and how ?
→ Insulin stimulates glucose uptake by tissues
→ Inhibits hepatic glucose production
What are the 2 types of diabetes?
→ Type 1 - insulin deficiency
→ Type 2- insulin insufficiency combined with insulin resistance
What are the major insulin sensitive tissues?
→ Liver
→ Skeletal muscle
→ Adipose tissue
Where does glucose go if it is in excess?
→ Lipogenesis
What do chylomicrons and VLDLs transport?
Transport TGs in the blood
What do fatty acids get packaged into when they are absorbed from food?
→ FFA taken up and packaged into chylomicrons from food
What is the main metabolic pathway in adipose tissue?
1) chylomicrons get changed into FFA by LPL
2) FFA re esterified stimulated by insulin for storage
3) glucose in circulation taken up stimulated by insulin
by GLUT 4 (when there is excess)
4)lipogenesis occurs
5) Adrenaline makes triglycerides break down and exported to circulation for use in energy metabolism
What are newly synthesized fatty acids packaged into from the liver?
→ new fatty acids synthesized by the liver -lipogenesis
→ get packaged into VLDLs
What is needed for uptake of fat into tissues for metabolism or storage?
→LPL
→to get TG into the cell from chylomicrons you need LPL to turn it back into TG
Describe the major metabolic pathway in muscle
1) Insulin stimulates glucose uptake into muscle GLUT 4
2) used in TCA cycle
3) in excess it is stored as glycogen
Describe the metabolic pathway of glucose and amino acid metabolism in the liver
1) Gluconeogenesis is stimulated by glucagon and inhibited by insulin
2) in the presence of glucagon amino acids enter gluconeogenesis or ketogenesis
In the presence of insulin what happens to acetyl CoA?
→ lipogenesis
In the presence of insulin what happens to the glucose in the liver?
→ lipogenesis
→produces malonyl CoA which is an intermediate
In the absence of insulin what happens to the glucose in the liver?
→ beta oxidation stimulated by glucagon
What can happen to the fatty acids entering the liver?
→ Esterified for transport and storage as TG
→ enter mitochondria for beta oxidation
What does beta oxidation of FA produce?
→ Acetyl CoA
What can acetyl CoA do?
→ enter TCA cycle
→ Ketogenesis
What does an excess of ketone bodies in the blood do?
→ overwhelms the buffering capacity
→ Leads to metabolic acidosis
What happens in diabetic ketoacidosis?
→ Decreased serum bicarbonate
→ Deep sighing
What does an absence of insulin result in?
→gluconeogenesis and beta oxidation are running unopposed
→Beta-oxidation of FA produces acetyl Co A, →combines with oxaloacetate (OAA) to form citrate, entering the TCA cycle for complete oxidative phosphorylation
→OAA is also used as a substrate in gluconeogenesis
→In absence of sufficient OAA, acetyl Co A builds up and is funnelled into ketogenesis
What is the role of insulin and glucagon in FA metabolism?
partition FA metabolism between lipogenesis and TG synthesis
Stimulation of lipogenesis (insulin) prevents FA entry to mitochondria, inhibiting beta oxidation
What does insulin indirectly inhibit?
inhibits B-oxidation
What are the two ways to increase GLUT4 density in muscle cell membrane?
(1) presence of insulin
(2) the process of muscle contraction
during exercise insulin levels normally decrease, but the contraction induced increase in GLUT4 allows continued glucose uptake
What is the enzyme that allows VLDL/TAG to enter adipose tissue?
lipoprotein lipase stimulated by insulin
Which is the most important buffer in rise of plasma glucose?
Skeletal muscle (large mass)
Which is most important for controlling plasma glucose during fasting phase?
liver
What type of cells in the pancreas produce beta cells?
alpha islet of Langerhans
What are the glucose sparing mechanisms?
Lipolysis
Beta-oxidation
Ketogenesis
