Endocrine control of metabolism Flashcards
Give an overview of energy metabolism
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What nutrients are circulated and what nutrients are stored?
Circulating: Glucose Fatty acids (FFA, NEFA) Amino acids Ketone bodies Lactate
Stored:
Glycogen
Triglycerides (TG, TAG)
Body proteins
What is the normal blood glucose concentration?
Around 5 mmol L-1
Define hyperglycemia and hypoglycemia?
Hyperglycemia: chronic exposure to raised glucose concentrations leads to protein damage via non-enzymatic glycation
Hypoglycemia: ultimately coma and death
< ~2.5 mmol L-1 is critical
How much glucose do the brain and skeletal muscle use?
Brain = 30mmol hr -1
Skeletal muscle = 300mmol hr-1
Where do we get glucose from?
Diet
Organs that can export glucose into the circulation
What prevents plasma glucose surging after a meal and plummeting between meals?
Hormones regulate the integration of carbohydrate, fat and protein metabolism to maintain constant plasma glucose levels.
What happens to nutrients in the fasting and absorptive phases?
What does insulin promote?
What hormones promote nutrient release?
How does insulin stimulate nutrient storage?
- Storage of nutrients in the absorptive phase (fed state)
Release of nutrients in the fasting phase (between meals) - Insulin: promotes storage, decreases plasma glucose
- Glucagon
Adrenaline (epinephrine)
Cortisol, growth hormone (somatotrophin)
Uptake of glucose by skeletal muscle, adipose and other tissues
Glycogen synthesis in liver, skeletal muscle,
Uptake of FA and amino acids
How does insulin inhibit nutrient release?
Inhibits nutrient release
Inhibits release of glucose from liver (hepatic glucose production)
Inhibits fat and protein breakdown (lipolysis and proteolysis)
Where is glucagon produced and what does it stimulate?
Where is adrenaline produced and what does it stimulate?
What does cortisol stimulate?
I.e Glucagon, Adrenaline and Cortisol
Stimulate pathways leading to energy release
Glucagon:
principal effects in liver
Stimulates hepatic glucose production
Adrenaline (and sympathetic NS):
Stimulates hepatic glucose production
Stimulates lipolysis: release of FA from adipose tissue stores
Cortisol:
Stimulates hepatic glucose production
Stimulates proteolysis: release of amino acids from body proteins (skeletal muscle)
What metabolic pathways serve as energy storage?
Glycogenesis
Synthesis of glycogen from glucose
Lipogenesis
Synthesis of FA from acetyl CoA
Triglyceride synthesis
Esterification of FA for storage as TG
What metabolic pathways serve as energy release?
Define: Glycogenolysis Gluconeogenesis Lipolysis Beta-oxidation Ketogenesis
Glycogenolysis
Release of glucose from glycogen stores
Gluconeogenesis
De novo synthesis of glucose from non-carbohydrate substrates
Lipolysis
Release of FA from TG breakdown
Beta-oxidation
FA to Acetyl Co A
Ketogenesis
Production of ketone bodies from Acetyl CoA
Describe the metabolic response to hypoglycemia
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What are the short, medium and long term defences against hypoglycaemia?
In the short-term:
Glucagon
Epinephrine
Sympathetic NS
In the medium-term:
Ketogenesis: fat reserves can provides a partial substitute for glucose, sparing muscle tissue from the destruction that would otherwise be needed to provide amino acid substrates for gluconeogenesis
In the long-term:
Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis
What are the defences against hyperglycemia?
What is type 1 DM?
What is type 2 DM?
Insulin
- Stimulates glucose uptake by tissues
- Inhibits hepatic glucose production
Lack of insulin action leads to hyperglycaemia, diabetes mellitus
Type 1 DM: insulin deficiency
Type 2 DM: insulin insufficiency combined with insulin resistance
Describe the metabolic pathway involving glucose and the effects of stimulating insulin
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What are the major metabolic pathways in adipose tissue?
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What is gluconeogenesis stimulated by?
What does gluconeogenesis form?
Stimulated by glucagon and inhibited by insulin
Amino acids are converted to ACETYL COA, pyruvate or enter the TCA cycle. It is then converted to oxaloacetate then to phosphoenol pyruvate then to glucose 6 phosphate
Describe the process of fatty acid metabolism in the liver
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Describe the process of fat metabolism and ketogenesis
What can fatty acids be used/ turned into when entering the liver?
What does beta-oxidation of fatty acid produce?
What happens to the product of beta-oxidation?
What 2 ketones are formed during ketogenesis?
How can ketones be used to produce energy?
Fatty acids entering the liver may be esterified for transport and storage as TG, or enter mitochondria for beta-oxidation
Beta-oxidation of FA produces acetyl Co A
Acetyl Co A may enter TCA cycle, or enter ketogenesis, depending on nutritional / hormonal status
Ketogenesis: synthesis of acetoacetate and hydroxybutyrate (ketone bodies) from Acetyl Co A
Ketone bodies are freely transported in blood stream, reconverted back to acetyl CoA, in brain and other tissues, and metabolised in TCA cycle for energy
Describe the process of ketogenesis
What happens when Acetyl CoA combines with oxaloacetate (OAA)?
What can this enter and then do?
What is OAA also a substrate for?
What happens in the absence of OAA?
What can lots of ketone bodies cause? RESP
In the liver, oxidation of fatty acids and gluconeogenesis can compete for substrates
- Beta-oxidation of FA produces acetyl Co A, which combines with oxaloacetate (OAA) to form citrate, entering the TCA cycle for complete oxidative phosphorylation
- However, OAA is also used as a substrate in gluconeogenesis
- In absence of sufficient OAA, acetyl Co A builds up and is funnelled into ketogenesis
Ketone bodies are acids: excess in circulation overwhelm buffering capacity of blood, leading to metabolic acidosis
What occurs in diabetic ketoacidosis?
In insulin deficiency (i.e. type 1 diabetes mellitus) the buffering capacity is overwhelmed
decreased serum bicarbonate
diabetic ketoacidosis
Normally ketones (acids) are buffered by the blood
deep sighing (Kussmaul) respiration
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