Lipid Metabolism Flashcards
Why are NEFA bound to proteins usually?
- Because they are toxic to cells
- Long chain FA are almost always esterified and bound to proteins otherwise they will form toxic micelles
Two sources of NEFA
- From dietary fats via exogenous pathway
- Synthesized via endogenous pathway
Most abundant FA
Long chain FAs
Myristic acid
- C14
- No double bonds
- 14:0
Palmitic acid
- C16
- No double bonds
- 16:0
Palmitoleic acid
- C16
- One double bond
- 16:1Δ9
- 16:1ω-7
Stearic acid
- C18
- No double bonds
- 18:0
Oleic acid
- C18
- One double bond
- 18:1Δ9
- 18:1ω-9
Linoleic acid
- C18
- Two double bonds
- 18:2Δ9,12
- 18:2ω-6
Linolenic acid
- C18
- Three double bonds
- 18:3Δ9,12,15
- 18:3ω-3
Arachidonic acid
- C18
- Four double bonds
- 20:4Δ5,8,11,14
- 20:4ω-6
Significance of bile
- Acts as a detergent in TG digestion
- Emulsifies TG and other lipids including fat-soluble vitamins (ADKE)
Lipases
- Hydrolyze ester bonds in TG
- Lingual and gastric lipases work in mouth and stomach: acidic pH optimum
- Pancreatic lipase hydrolyzes most TG. Works in small intestine (D and J). Optimum pH around 7.
Colipase
- Allows lipase access to lipid substrates
- Secreted as inactive precursor by pancreas and activated in duodenum thru the action of trypsin
- Stabilizes the open position
Pancreatic lipase
- Esterase with optimum pH 7
- Partial hydrolysis of TG containing long chain FA
- Preference for 1 and 3 positions
- Main products and 2-MAG and NEFA
Bile components
- Bile acids (salts)
- Phosphatidlycholine
- Cholesterol
Mixed micelles
- Formed by bile acids with the nonpolar digestion products (2-MAG and NEFA)
- Allow translocation across aqueous boundary layer at intestinal wall (absorption)
- Glycerol backbones oriented toward aqueous phase
FATP5
- Fatty Acid Transport Protein 5
- Major FA transporter in enterocytes
- Carrier-mediated transport
AQP3
- Mediates glycerol transport
- Member of aquaporin family
Steatorrhea definition and causes
- Excessively fatty stools
- Failure of bile production or blockage of bile flow
- Exocrine pancreas dysfunction or obstruction of pancreatic duct
- Failure of uptake into intestinal mucosal cells (enterocytes)
Chylomicrons
- Lipoprotein particles that are exported into the lymph
- TG resynthesized from 2-MAG and then packaged into chylos
- Also contains: cholesterol esters, apolipoprotein B48, phospholipids, and cholesterol
- Makes serum look milky after a fatty meal
Intestinal FA-binding protein
-Binds LCFAs once their inside the enterocytes
Acyl-CoA synthetase
- Also called thiokinase
- Catalyzes formation of acyl-CoA derivatives of LCFA
Acyltransferases
- Transacylases
- Catalyze transfer of 2 LCFA moieties to 2-MAG
Site of absorption of SCFAs
- In the colon
- Some bacteria in the colon produce SCFAs
- Most secreted in feces
Apolipoproteins
- Amphipathic proteins
- Added in mature chylomicrons after being released into the bloodstream
Apo-B48
- Principal protein component of nascent chylomicrons
- Added in the intestinal mucosa
Lipoprotein lipase
- Chylomicron clearance
- FAs release from the lipoproteins
- Located in capillary endothelial walls of various tissues (muscle and adipose especially)
- Cleavage at all 3 ester bonds
- Products are glycerol and NEFA
- Needs C2 to recognize chylomicrons
- Insulin promotes release of lipoprotein lipase from adipocytes and muscle–increased hydrolysis and uptake–used as fuel or stored
