Endocrine control of metabolism Flashcards
(21 cards)
give an overview of energy metabolism
-the TCA cycle and acetyl coA are the core of energy metabolism. This means any molecule that can be metabolised into acetyl-coA can be fed into the cycle
-glucose and amino acids form acetyl CoA through a series of steps
-fatty acids through B-oxidation and ketone bodies can also form acetyl CoA.
-lactate forms pyruvate which then forms acetyl CoA.
explain which nutrients are stored and circulating
Stored:
-glucose
-fatty acids
-amino acids
-ketone bodies
-lactate
Circulating:
-glycogen
-triglycerides from fatty acids
-body proteins
Explain the consequences of hypoglycaemia and hyperglycaemia
-the brain depends on glucose metabolism so hypoglycaemia can cause coma and death.
-critical hypoglycaemia <2.5mmol L-1 is critical
-hyperglycaemia; chronic exposure to raised glucose concentrations lead to protein damage via non enzymatic glycation
explain the amount of glucose needed in the body
-60% of body weight is water, 40% is ICV and 20% ECV
-the brain requires 30mm/hr so this would last it more than two hours
-skeletal muscle during exercise requires 200mmol/hr so this would last less than an hour (15 minutes roughly)
what prevents plasma glucose surging after a meal and plummeting between meals
-hormones regulate hte integration of carbohydrate, fat and protein metabolism to maintain constant plasma glucose levels.
explain the two phases of metabolism
the two phases of metabolism are the absoptive and fasting phase
-during the fed state, nutrients are being absorbed
-in the fasting state between meals, nutrients are being released.
explain the major effects of insulin
stimulates nutrient storage:
-uptake of glucose by skeletal muscle, adipose and other tissues.
-glycogen synthesis in liver, skeletal muscle
-uptake of FA and amino acids into adipose and muscle tissue
Inhibits nutrient release:
-inhibits release of glucose from liver (hepatic glucose production)
-inhibits fat and protein breakdown (lipolysis and proteolysis)
explain major effects of counter-regulatory hormones
Glucagon:
-principle effects in liver
-stimulates hepatic glucose production
Adrenaline:
-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
explain metabolic responses to hypoglycaemia
1) secretory cells in the pancreas sense hypoglycaemia and signal the CNS
2) an increase in sympathetic activity causes Ach release which acts on the liver and pancreatic cells to release glucagon, produces more glucose and stimulates lipolysis
short term responses:
-glucagon release
-epinephrine release
-sympathetic CNS
long term responses:
-cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis
explain defences against hyperglycaemia; insulin
lack of insulin action leads to hyperglycaemia, diabetes mellitus
* type 1 DM; insulin deficiency
* type 2 DM; insulin insufficiency combined with insulin resistance
explain stimulates and inhibitors of hyperglycaemia
stimulants:
-liver;
* glycogenesis
* glycolysis
* lipogenesis
* adipose tissue- glucose uptake, free fatty acid uptake and lipogenesis
inhibits:
-liver; glycogenlysis, gluconeogenesis
-adipose tissue; lipolysis
explain what happens during the absorptive state and post absoprtive state
1)Absorptive state:
-blood glucose rises and it enters the liver cells via the GLUT transporters. It’s automatically converted to G6P which maintains the concentration gradient for entry
-it then forms pyruvate and enters the TCA cycle (glycolysis) or forms glycogen (glycogenolysis)
-excess glucose can then be converted to fatty acids via lipogenesis which can be stored as fat.
2) Post absorptive state:
-insulin release is stopped and glucagon is released, it stimulates the nutrient releasing pathways to stop blood glucose from falling too low.
-glycogen is then reconverted into G6P and then glucose ‘
-some amino acids are converted into pyruvate and then glucose in gluconeogenesis.
-fat is mobilised and lipolysis also occurs
give an overview of the transport and turnover of lipids in the body
-lipids are not soluble so are transported as lipoproteins in the plasma
-chylomicrons and VLDLs transport TAGs in the blood to the liver, adipose tissue in the absorptive phase.
-the transported fat (TAGs) are broken down at the endothelial membrane by lipoprotein lipase into free fatty acids and glycerol.
-the resulting fatty acids are then taken up by the adipocytes and liver and resynthesised into TAGs for storage or for energy metabolism.
-new fatty acids synthesised in the liver by lipogenesis are packaged into LDL
-as the chylomicron/VLDL passes the lipoprotein lipase, the TAG will be broken down.
-the fatty acids are absorbed by the adipocyte and esterified into triglycerides
-at the same time, excess glucose from the circulation is taken up by the insulin dependent GLUT4 transporter.
-finally it is converted into acetyl CoA which is then converted into fatty acids during lipogenesis
explain major metabolic pathways in skeletal muscle
-as insulin levels rise, the expression of GLUT4 transporters on the cell membrane increases. This increases glucose permeability so more is taken up. Amino acid uptake also increases as does fatty acid uptake through LPL.
-glucose moves in and is phosphorylated, its then converted into glycogen or into pyruvate for energy metabolism
-pyruvate can be fed into the TCA cycle or it can be converted into lactate when we respire anaerobically.
-lactate can move to the liver for gluconeogenesis.
explain glucose and amino acid metabolism in the liver
-when we want to mobilize fats from the lipid stores. TAGs are broken down into fatty acids by LPL. During beta oxidation, fatty acids are converted into acetyl CoA which is fed into the TCA cycle
-when fatty acid oxidation and gluconeogenesis are happening simultaneously, there is competition for oxaloacetate. Oxaloacetate is needed for acetyl coA to enter the TCA cycle in b-oxidation and for gluconeogenesis.
-Ketogenesis converts the acetyl coA into ketone bodies which are then used for energy by muscle, this conserves glucose for the brain and reduces the demand for amino acids for gluconeogenesis so there’s less protein breakdown.
explain fatty acid metabolism in the liver
-fatty acids enter the cells and are converted into fatty acetyl coA
-this enters the mitochondrion via the transporter CPT to be converted into acetyl CoA which are then used to form glucose.
-insulin inhibits the CPT transporter so less glucose is produced and there’s less ketogenesis. Malonyl CoA also inhibits this transporter so inhibits B-oxidation
-this fatty acetyl CoA can also reform triacyl glycerides and can be packaged into LDLs
explain fat metabolism and ketogenesis
-fatty acids entering the liver may be esterified for transport and storage as TG or to enter mitochondria for beta oxidation.
-beta oxidation of FA produces acetyl CoA which can then enter the TCA cycle or enter ketogenesis depending on nutritional/hormonal status.
-ketogenesis; synthesis of acetoacetate and hydroxybutyrate from acetyl CoA.
-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
explain the process of ketogenesis
-in the liver, oxidation of fatty acids and gluconeogenesis can complete for substrates.
-beta oxidation of FA produces acetyl CoA, which combines with oxaloacetate to form citrate, entering the TCA cycle for complete oxidation phosphorylation.
-however, OAA is also used as a substrate in gluconeogenesis.
-in absense of sufficient OAA, acetyl CoA builds up and is funelled into ketogenesis.
-ketone bodies are acids; excess in circulation overwhelm buffering capacity of blood, leading to metabolic acidosis
explain diabetic ketoacidosis
-normally, ketones are buffered by the blood and in insulin deficiency the buffering capacity is overwhelmed. This is known as diabetic ketoacidosis.
-there causes decreased serum bicarbonate and deep sighing respiration.
-Kussmaul’s breathing is a deep and laboured breathing that aims to remove excess CO2 from the blood to combact acidosis
give an overview of metabolic disturbances in diabetes mellitus
-hyperglycaemia occurs when there is an excess of glucose that isn’t being taken up by the cells and the body makes more glucose via gluconeogenesis
-this increases GFR which results in glycosuria and increases osmolarity in the tubules, resulting in less water being reabsorbed and more being excreted.
-this causes dehydration and impairs kidney function, the impaired kidney function means less H+ is excreted causing acidosis.
