LECTURE 4 (Lipid synthesis) Flashcards
What are the properties of Fatty acids & triglycerides?
- Most lipids degraded to FREE FATTY ACIDS in intestine
- Enterocytes convert fatty acids into TRIACYLGLYCEROL
- When triacyglycerols reach the tissues to be used/stored, they are degraded back to free fatty acids
What is the form that fatty acids are transported through the plasma in?
Chylomicrons
Where is Lipoprotein lipase found?
- On endothelial surfaces of capillaries
- Abundant in adipocytes and muscle tissue
Where does Fatty acid synthesis take place?
- Liver
- Mammary glands
- Adipose tissue (small amount)
[excess carbohydrates and proteins -> fatty acids]
Where is fatty acid stored?
Adipose tissue
[where it’s stored as triglycerides]
How are fatty acids broken down?
Fatty acids are OXIDISED through fatty acid/β-oxidation into TWO-CARBON ACETYL CoA molecules, which can then enter the KREBS CYCLE to generate ATP.
Which two enzymes are used in Fatty acid synthesis?
- Acetyl-CoA carboxylase (ACC)
- Fatty acid synthase (FASN)
What are the properties of Fatty acid synthesis?
- Occurs in high energy states (fed state)
- Lots of acetyl-CoA -> lots of ATP
- Inhibition of ISOCITRATE DEHYDROGENASE ->. high CITRATE level inside the cell
Describe what happens in Fatty acid synthesis
1) Citrate moves from MITOCHONDRIA to CYTOSOL via CITRATE SHUTTLE
[since Acetyl-CoA cannot cross membrane]
2) Citrate is converted into acetyl-CoA via ATP-CITRATE LYASE which causes excess acetyl-CoA to move to the cytosol
3) Acetyl-CoA is converted to MALONYL-CoA via ACETYL-CoA CARBOXYLASE [RATE LIMITING STEP!]
4) Synthesis of PALMITATE which requires FATTY ACID SYNTHASE and NADPH -> uses carbons from ACETYL-CoA and MALONYL-CoA to create a 16-carbon fatty acid (PALMITATE)
Which co-factors are required to convert Acetyl-CoA into Malonyl-CoA?
- Citrate
- Insulin
- Glucagon
- Epinephrine
- Biotin
What is Biotin?
A co-factor for carboxylation enzymes that add 1-carbon group via CO2
Which Carboxylation enzymes require Biotin?
- Pyruvate carboxylase
- Acetyl-CoA carboxylase
- Proprionyl-CoA carboxylase
What are the major sources of NADPH required for fatty acid synthesis?
- Conversion of MALATE to PYRUVATE
- Conversion of GLUCOSE-6-PHOSPHATE to RIBULOSE-5-PHOSPHATE
How can fatty acid chains be further elongated?
- Addition of 2-carbon units in the SMOOTH ENDOPLASMIC RETICULUM (SER) where MALONYL-CoA is the 2-carbon donor and NADPH supplies the electrons
- BRAIN has elongation capabilities allowing it to produce the very-long-chain fatty acids (over 22 carbons) required for synthesis of lipids
Glucose transporter in adipocytes (GLUT-4) is _________-_________
Insulin dependent
Can Palmitate be modified to other fatty acids?
YES
What happens when plasma glucose and plasma insulin levels are low?
Adipocytes have only limited ability to synthesise glycerol phosphate and cannot produce Triacylglycerides
Where can glycerol phosphate be synthesised?
- Liver
- Adipose tissue
What are the properties of Saturated fats?
- Contains no double bonds
[“saturated” because saturated with hydrogen] - Usually solid at room temperature
- Raise LDL cholesterol
What are the properties of Unsaturated fats?
- Contains at least one double bond
- Monounsaturated/Polyunsaturated
What are the properties of Trans fat?
- Trans from partial hydrogenations (food processing method)
- Increase LDL, lower HDL
Most natural fats have which configuration? (Cis/Trans)
Cis
Describe Omega-3 fatty acids
- Type of polyunsaturated fat
- Found in fish oil
- Can be incorporated into cell membranes
What are the benefits of Omega-3 fatty acids?
- Consumption associated with decreased cardiovascular event
- Reduce VLDL production
- Lowers triglyceride levels
- Modest increase in HDL
- Commercial supplements available (LOVAZA)
What are the GI side effects of Omega-3 fatty acids?
- Nausea
- Diarrhoea
- “fishy” taste
