Lipid Metabolism Flashcards
What are essential fatty acids?
Fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesise them
What are essential fatty acids precursors for?
Eicosanoids (prostaglandins, leukotrienes, thromboxanes)
What is cholesterol essential in the production of?
- Membranes - Vitamin D - Steroid hormones - Bile salts
How does cholesterol lead to the formation of steroid hormones?
Cholesterol is the precursor of the five major classes of steroid hormones
What are the 5 main classes of steroid hormones?
- Androgens (e.g. testosterone) 2. Oestrogens 3. Progestogens (e.g. progesterone) 4. Mineralocorticoids (e.g. aldosterone) 5. Glucocorticoids (e.g. cortisol)
How does cholesterol lead to the formation of bile salts?
Bile salts are synthesised in the liver from cholesterol
What are chylomicrons?
Lipids from the diet - a droplet of fat present in the blood or lymph after absorption from the small intestine.
Where are chylomicrons formed?
In intestinal epithelial cells
Where are chylomicrons released into?
The lymph
How do chylomicrons enter the circulation?
Via thoracic duct, into subclavian vein (Do not pass directly from the GI tract to the liver)
Where does cholesterol in your body come from?
- Synthesis (in almost all tissues but mainily in liver and intestine)
- Diet (eggs, liver, meat)
What is the role of lipoproteins?
Transport lipids such as triglycerides, phospholipids, and cholesterol
When lipoprotein lipase breaks down triglycerides, what does it from?
Free fatty acids either for energy production (muscle) or storage (adipose tissue)
Lipid pathway diagram
How do fatty acids arrive at peripheral tissue?
- In chylomicrons or VLDL
- From adipose tissue
How are fatty acids released from chylomicrons or VLDL?
By lipoprotein lipase
How are fatty acids released from adipose tissue?
- triacylglycerols broken down by hormone sensitive lipase
- fatty acids released into blood
- transported to tissues bound to albumin
Can fatty acids be used by the brain?
No - cannot cross the blood brain barrier
Brain uses glucose
What happens during fasting?
Fatty acids released from adipose tissue
Describe the oxidation of fatty acids
- Activation of fatty acyl CoA in cytosol (FA CoA released from CoA, attached to carnitine. Occurs on outer mit membrane)
- Beta oxidation takes place in mitochondria (transport across membrane)
- Long chain fatty acids require carnitine for transport
Where does carnitine transport fatty acids?
Across the inner mitochondrial membrane
What is the carnitine transport system inhibited by? What is purpose of this?
Malonyl CoA
Prevents sythesis and degredation of fatty acids at the same time
Describe the spiral process of the beta oxidation of fatty acids
- Each turn released 1 acetyl CoA, produces NADH and FADH2
- Completely aerobic process
What happens to the NADH and FADH2 produced by the beta-oxidation of fatty acids?
Oxidised by electron transport chain
What happens to the acetyl CoA produced in the beta oxidation of fatty acids?
Enters Krebs cycle - producing more NADH/FADH
What is the beta oxidation of fatty acids dependent on?
Also note no ATP produced by this cycle itself so entirely dependent on krebs and etc for energy production – i.e. totally dependent on oxygen
What is fatty acid oxidation largely regulated by?
By access of fatty acids to the mitochondria – this is controlled by the concentration of malonyl CoA
What is the frist step of fatty acid synthesis?
Malonyl CoA is formed by acetyl CoA carboxylase
What does high [malonyl CoA] inhibit?
Inhibits carnitine acyl-transferase-1
This ensures that fatty acid breakdown is inhibited when energy is plentiful
What are ketone bodies formed from?
Excess acetyl CoA
Where does ketone synthesis occur?
In the mitochondria of liver cells under conditions where the body relies on fatty acid oxidation for energy
When does the body rely on fatty acid oxidation for energy?
- Fasting
- Uncontrolled diabetes (ketoacidosis)
Where are ketones released into?
Into the blood and oxidised to produce energy in peripheral issues including brain tissue
Describe cholesterol uptake from LDL
- LDL binds to receptor on cell surface and are taken up into cell
- Cholesterol is released
- Receptors are recycled
What is effect of lack of receptors on cholesterol uptake from LDL?
Lack of receptors will prevent LDL uptake
What is LDL receptor synthesis controlled by?
Level of cholesterol in cell
What are the 4 steps of cholesterol biosynthesis?
- Acetyl CoA to mevalonate (C6)
- Mevalonate to phosphorylated isoprene units (C5) –> activation
- Polymerise 6 isoprene units to form C30 chain (squalene)
- Cyclisation to form ring structure (lanosterol) then cholesterol
What stage in cholesterol biosynthesis controls the rate of synthesis?
1 - Acetyl CoA to mevalonate (C6)
Where does cholesterol biosynthesis occur?
In cytosol and smooth endoplasmic reticulum
