Kerry Loomes-4 Flashcards
What are the major producers of fat?
Liver and fat cells
What are adipocytes?
Specialised cells of adipose tissue where triglycerols is stored and mobilised
Adipose tissue is the largest storage organ and weighs approximately 10-15 kg in a young adult holding 135,00 kcal or 200 meals
Where are most triglycerides obtained from during the fed state?
Mostly from the diet, with the liver synthesizing 1-5% and 1-2% of fatty acids being made de novo in adipocytes
How is fat synthesized by glucose by the liver?
Glycolysis operates in partnership with the pentose phosphate pathway
This occurs when ATP and citrate are high and then glucose-6P is driven down the pentose phosphate pathway leading to NADPH production
NADPH along with Malonyl CoA produced from Acetyl coA is used in lipogenesis
What is the role of phosphofructokinase in fat synthesis?
If phosphofructokinase is inhibited then glucose-6P is shunted to the pentose phosphate pathway to drive lipid synthesis
This inhibition occurs from citrate
Promotion occurs from xylulose-5P from the pentose phosphate pathway which will result in both glycolysis and the pentose phosphate pathway occurring at the same time in the cell which is necessary as products of both cycles are needed for lipid synthesis
How does the pentose phosphate pathway regulate lipid synthesis?
The production of xylulose 5-phosphate by the pentose phosphate pathway stimulates phosphofructokinase via an increase in fructose-2,6-bisphosphate mediated by protein phosphatase 2A removing a phosphate group from PFK2F- 2,6- bisphosphate
How are the enzymes involved in lipogenesis regulated?
Xylulose-5P activates the transcription factor ChREBP so PPA2 can act on it in order to remove phosphate groups, allowing it to enter the nucleus regulate transcription and upregulate the expression of lipogenic enzymes
What is the effect of insulin on adipocytes in the fed state?
Increase the uptake of glucose through increasing the blood glucose level which supplies the adipocytes as well as causing the adipocyte to move internalized glucose transporters to its membrane
How does glucose generate triglyceride in adipocytes?
Glycolysis proceeds up to the point of dihydroacetone which is converted to glycerol-3P which combines with fatty acids to generate the triglyceride molecule
Why are adipocytes unable to produce fat if insulin is absent?
Glucose is unable to enter the cell
How is fat broken down in adipocytes in the fasted state?
Triglycerides are broken down by hormone sensitive lipase which is stimulated by epinephrine and norepinephrine
Lipid break down produces Free fatty acids and glycerol.`
What happens to free fatty acids after the lipid has been broken down?
Transported via albumin in the blood to the muscle
What happens to glycerol after the lipid has been broken down?
Glycerol passes out of the cell where it is taken to the liver which has the glycerol kinase enzyme which can regenerate the glycerol-3P
How is fat synthesis and fat breakdown prevented from generating a futile cycle in adipocytes?
Insulin leads to the activation of Acetyl coA carboxylase and the inactivation of hormone sensitive lipase
What are the two key enzymes in the adipocyte for controlling lipid biosynthesis and breakdown?
Acetyl CoA carboxylase which catalyses conversion from acetyl coA to malonyl coA which can be turned off via phosphorylation
Hormone sensitive lipase converts the triglyceride to free fatty acid and glycerol this is activated via phosphorylation
