Fatty Acid Metabolism I Flashcards
What are the 3 classes of lipids?
- Free fatty acids
- Triglycerides
- Cholesterol
- Cholesterol esters
Describe the characteristics of the “fasting state”
- Glucagon ↑
- Glycogenolysis ↑
- Gluconeogenesis ↑
- Fatty acid oxidation ↑
- Glycolysis in liver ↓
- Glycogenesis ↓
- Fatty acid biosynthesis ↓
Describe the characteristics of the “fed state (after a meal)”
- Insulin ↑
- Glycolysis ↑
- Glycogenesis ↑
- Fatty acid biosynthesis ↑
- Glycogenolysis ↓
- Gluconeogenesis ↓
- Fatty acid oxidation ↓
What gives us the drive to eat?
- Ghrelin
- Peptide hormone released by the stomach
- Acts in the hypothalamus of the brain
Tells the brain to tell your body that you are hungry
What makes triglycerides very hydrophobic?
- The structure
- Triglycerides = T-shaped
- All of the non-polar parts are on the ends
What does the body produce in order to emulsify lipids?
Bile
Describe bile
- Synthesized in the liver
- Stored in the gall bladder
- Amphipathic
- Acts as a detergent that coats lipids and breaks them into smaller pieces
What is the purpose of pancreatic lipase?
- Enzyme secreted by the pancreas
- Cleaves triglycerides at the 1 and 3 position
- The result is 2 fatty acids and a monoacylglycerol (these can be absorbed directly into the cells of the small intestine)
What happens to triglycerides after they are cleaved by pancreatic lipase?
- The 2 fatty acids and monoacylglycerol are absorbed into the cell where they are converted back into triglycerides
- Cholesterol = converted into cholesterol esters (extremely hydrophobic)
How do the cholesterol esters and triglycerides (which are extremely hydrophobic) make their way out of the cells of the small intestine and into circulation?
Chylomicrons
Describe the structure and function of chylomicrons
- Contains inner core filled with triglycerides and cholesterol esters
- Outside layer = phospholipid monolayer
- Surface contains multiple proteins
What important protein (the you must remember) is located on the surface of chylomicrons?
ApoC-II
Once chylomicrons have been generated, how are the triglycerides hydrolyzed back into fatty acids so that they can be taken up by the cell?
Lipoprotein Lipase
Describe the function of lipoprotein lipase
- Enzyme that lines the endothelium of capillaries surrounding adipose and muscle tissue
- Cleaves triglycerides within chylomicrons into fatty acids and monoacylglycerides
- The fatty acids and monoacylglycerides can then be taken up by the adipose tissue for storage or the ,muscle tissue for energy
What is the purpose of ApoC-II
Activate LPL increasing triglyceride hydrolysis
What happened to chylomicron remnants once the triglycerides from the inner core have been broken down?
They are taken up by the liver
What happens in individuals that do not have lipoprotein lipase?
- They have excess chylomicrons in their blood stream
- Symptoms include:
- Loss of appetite
- Abdominal pain
- Nausea
- Vomiting
How are fatty acids stored?
Intracellular lipid droplets
Describe the structure of lipid droplets?
- Structurally similar to chylomicrons
- Inner core = triglycerides and cholesterol esters
- Outer core = phospholipid monolayer
Describe what happens to stored lipids in the fasting state
- Lypolyisis is stimulated
- 3 enzymes are involved in the cleaving of triglycerides
What are the 3 enzymes involved in cleaving triglycerides?
- Adipose triglyceride lipase (ATGL): cleave first fatty acid at the 1 position
- Hormone sensitive lipase (HSL): cleaves fatty acid at the 3 position
- Monoacylglycerol lipase (MAGL/MGL): generates the last free fatty acid and glycerol
How is lypolysis regulated?
Glucagon and epinephrin act on receptors in the adipose tissue that activate PKA (protein kinase A)
Describe the regulation of lypolysis
- After a meal you want PKA to be turned off
- If you are fasting you want PKA to be turned on
- PKA will posphorylate perilipin-1 and ABHD5
Describe the function of perilipin-1
- Located on the surface of the lipid droplet
- PKA = inactive: perilipin-1 binds to ABHD5 and sequesters it
- PKA = active: perilipin-1 will release ABHD5
- When ABHD5 = phosphorylated it will release ATGL to the surface of the lipid droplet
What other enzyme does PKA phosphorylate?
- HSL
- Phosphorylation of HSL brings the lipid droplet to the surface
What is an example of a disease that is associated with lipolysis disfunction?
Mutation resulting in nonfunctional ABHD5
