T2 L5 The liver & glucose homeostasis Flashcards
What are the functions of the liver?
1) Stores glycogen from ingested carbohydrates & other non carbohydrate precursors
2) Breaks down glycogen & release glucose when plasma glucose levels fall
3) Synthesises glucose from non-carbohydrate precursors for release to maintain plasma glucose
4) Synthesises ketone bodies & secretes them into the blood as fuel for other tissues
5) Deaminates surplus amino acids & converts the amino groups & ammonia to urea
6) Aids in elimination of cholesterol from the body & synthesises bile salts from cholesterol
7) Acts as storage depot for fat soluble vitamins
8) Major site for metabolism & elimination of drugs & toxic substances
What 3 body fuels are oxidised for ATP synthesis?
Glucose - stored as glycogen
Long chain fatty acids - stored as triacylglycerol
Amino acids - mainly present in proteins
What are the phases of assimilation?
1) Immediate absorptive events
2) Post absorptive events
What happens in the immediate absorptive events after a meal?
Immediate fate of dietary compounds
Liver & adipose tissue mainly take up materials = import
Some amino acids are used to synthesise proteins & some fat is used to synthesis membrane fats
What happens in the post-absorptive events after a meal?
Between meals the cells of the liver & adipose tissue export
Body must cope with decreased availability of metabolites in the blood, which requires metabolism of the reserves of glycogen built up during feeding
Why is the brain vulnerable to hypoglycaemia?
The cerebral cells mainly derive their energy from aerobic metabolism of glucose
What can’t cerebral cells do?
Store glucose in significant amounts
Synthesise glucose
Metabolise substrates other than glucose or ketone bodies
Extract sufficient glucose for their needs from the extracellular fluid at low concentrations as glucose entry into the brain is not facilitated by hormones.
What is gluconeogenesis?
Glucose synthesis in the liver & kidneys from non-carbohydrate precursors such as amino acids, glycerol & lactate
What is glycolysis?
Oxidation of glucose by peripheral tissues
What is glycogenolysis
Mobilisation of glycogen stores in the liver
What does insulin do?
Increase glycolysis, glycogen & fat synthesis
What do glucagon, catecholamines, cortisol & growth hormone do to gluconeogeneis & glycogenolysis?
They increase it
How is glucose controlled via hormones?
Blood glucose doesn’t vary much throughout the day or night
Mainly controlled by fluctuations in circulating levels of insulin & glucagon
Alterations in the ratio of insulin: glucagon within the blood are essential for the maintenance of blood glucose
How long is glucose absorbed for after a meal?
2-3 hours from the small intestine
Glycogen is degraded between meals & stores last for 12-24 hours
What is the most important metabolic effect of insulin?
It stimulates the entry of glucose into cells
Transport of molecules can be passive or active
What are gluts?
A family of glucose transporter proteins that transport glucose into the cell.
What is glut 1?
Found in many tissues - erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue
Responsible for basal glucose uptake in most tissues
Increased in amount by glucose deprivation
Affinity is around 1mM
What is glut 2?
Found in liver, pancreatic beta cells, kidney & small intestine
High capacity
Low affinity at around 15-20mM
Only takes up glucose at high plasma conservation which conserves it for other tissues such as the brain
What is glut 3?
Found in the brain & is predominantly neuronal
Supplements glut in tissue with high energy demands
High affinity of 1mM which allows glucose uptake, irrespective of blood glucose concentration
What is glut 4?
Found in skeletal muscle, heart & adipose tissue (insulin-sensitive)
Insulin sensitive transporter
Affinity around 5mM so controlled by plasma glucose levels & number of transporters on the membrane
Lives in cytoskeleton of the cell & is only inserted into the membrane under the influence of insulin.
What is glut 5?
Found in the small intestine
Fructose transporter
Why does the liver only take up glucose when there is a high concentration?
To save glucose for the other organs
What are the immediate cellular effects of insulin?
Increases rate of glucose uptake in muscle & adipocytes
Modulation of the activity of enzymes involved in glucose metabolism
Occurs in minutes
Doesn’t require protein synthesis
What are the longer-lasting cellular effects of insulin?
Results from continued exposure to insulin
Increase expression of liver enzymes that synthesise glycogen
Increase expression of adipocyte enzymes that synthesise triacylglycerols
Inhibits lipolysis in adipose tissue by inactivating hormone-sensitive lipase which mobilises fatty acids from triglyceride stores
Functions as a growth factor for some cells such as fibroblasts
Effects occur over several hours
What are the 2 products of the pentose phosphate pathway?
Ribose phosphate
NADPH
What is ribose phosphate used for?
Used to synthesis RNA & DNA
What is NADPH used for?
Reductive biosynthesis & to maintain the redox balance of the cell
What does tripeptide glutathione?
It maintains the redox balance of the cell. Maintained in the reduced state using NADPH.
This is particularly important in erythrocytes
What is the pentose phosphate pathway?
Cytosolic pathway present in all cells
Branches from glycolysis at G-3-P
Describe glucose metabolism in the heart & muscle
Insulin-sensitive Glut 4 transporter
Stored as glycogen or used to produce energy
Describe glucose metabolism in the adipose tissue
Glut 4 transporter
Glycolysis produces acetyl CoA which can be used to produce ATP or synthesise fats
Some is used for the pentose phosphate pathway to produce NADPH
Describe glucose metabolism in the RBC
Glut 1 transport system
Glycolysis to form lactate produces energy
Some is used in the pentose phosphate pathway to produce NADPH for the maintenance of reduced glutathione.
RBC don’t have mitochondria so can’t fully oxidise glucose via the TCA cycle & ETC. Rely on glycolysis for their energy requirement
Describe glucose metabolism in the brain
Glut 1 & Glut 3 transport systems
Aerobic metabolism to produce energy
Some used in pentose phosphate pathway to provide NADPH for lipid synthesis
Describe glucose metabolism in the liver
Glut 2 transport system
Stored as glycogen, glycolysis to form pyruvate & then acetyl CoA
Some produces ATP & excess acetyl CoA used for fat synthesis
Some glucose goes through pentose phosphate pathway to form NADPH to support fat biosynthesis.
