Intro to Lipids and Their Metabolism - RM Flashcards
What are the complexities of lipids and their metabolism related to?
their heterogeneity and water insolubility
What is the major storage form of metabolic energy in humans? What is its structure?
triacylglycerides (TG), 3 C backbone of glycerol with the 3 OH groups esterified to fatty acid chains
How does length of R group affect the solubility of triglycerides?
short R groups, more soluble due to polarity of carboxyl groups
long R groups, more hydrophobic, less soluble
What is the 4 step overview of TG metabolism in intestine?
- digestion of TG into 2-MAG and fatty acids
- absorption of components into intestinal cells
- resynthesis of TG by intestinal cells
- assembly of TG into lipoproteins for export to lymph to blood
What are the 3 reasons to store metabolic energy as fat?
- carbons in TG have lower oxidation state (more highly reduced, has 2x as much energy per dry weight)
- stored in anhydrous state (carbs have bound water that adds to weight)
- don’t participate in osmotic balance (can be stored to large fraction of cell volume)
What is the structure of a fatty acid?
carboxylic acid with an alkyl side chain, normally chains of 16 or 18 carbons
What type of polyunsaturated hydrocarbon chains can a fatty acid not have?
ones with adjacent double bonds or conjugated double bonds because it would be too easily oxidizable
(usually separated by a methylene group)
What type of double bonds are found naturally occuring? Why?
cis, interferes with packing, lower Tm, keeps the membrane fluid
How are LCFAs kept from being toxic to cell (free, ionized LCFA)?
esterified or tightly bound to FA-binding proteins intracellularly or albumin extracellularly
Why do fatty acids have even numbers of carbons?
synthesized 2 carbons at a time
What cannot use fatty acids as fuel and why can’t it?
brain, free fatty acids can’t cross blood brain barrier
How are fatty acids used for fuel?
FA-derived acetyl coA enters citric acid cycle to give ATP and heat
What are the sources of non-esterified fatty acids (NEFA)?
dietary fat (TG) and fatty acids synthesized de novo by liver and adipocytes
How many carbons and double bonds in myristic acid?
14 C, 0 double bonds
How many carbons and double bonds in palmitic acid?
16 C, 0 double bonds
How many carbons and double bonds in palimtoleic acid?
16 C, 1 double bond
How many carbons and double bonds in stearic acid?
18 C, 0 double bonds
How many carbons and double bonds in oleic acid?
18 C, 1 double bond
How many carbons and double bonds in linoleic acid?
18 C, 2 double bonds
How many carbons and double bonds in linolenic acid?
18 C, 3 double bonds
How many carbons and double bonds in arachidonic acid?
20 C, 4 double bonds
What does bile contain?
bile acids, phosphatidyl choline, cholesterol
What do lipases do?
hydrolyze ester bonds in TG to release fatty acids
Why is bile needed?
emulsification of TG, lipids, and fat soluble vitamins to increase water-lipid interface to allow hydrophilic enzymes to get close enough to act upon them
How is pancreatic lipase activated?
formation of complex between colipase and droplet of emulsified lipid (stabilizes open conformation and allows access to substrate and shields against bile salts that inactivate enzyme)
Where is colipase secreted from? How is it activated? Why is it needed?
secreted as zymogen from pancreas, activated in duodenum by trypsin, needed for lipase to access substrate
Where does pancreatic lipase preferentially cleave?
1 and 3 positions of TG to release 2-MAG and 2 FAs
Why are bile acids needed for absorption?
form mixed micelles with nonpolar digestion products (2-MAG and FAs) and allow translocation across stationary aqueous boundary layer at intestinal wall
Where is the only place mixed micelles are found in the body?
intestinal lumen
What are bile salts dual function?
aid in digestion by emulsification and absorption by forming mixed micelles
Do bile salts enter the fat-absorbing enterocytes? If not, where are they absorbed?
No, abosrbed in distal ileum
What is FATP?
fatty acid transport protein, absorbs FAs into enterocytes
What does AQP3 mediate transport of into enterocytes?
glycerol
What fats can be absorbed without prior enzymatic digestion?
short and medium FA triglycerides in breast milk
cholesterol, vitamins A, D, K, E
What is steatorrhea? What is it caused by?
excessively fatty stools, failure of bile production or blockage of bile flow, exocrine pancreatic dysfunction or obstruction of pancreatic duct, malabsorption into enterocytes
How is TG resynthesized from 2-MAG and FFAs in intestinal cell cytoplasm?
acyl coA synthetase forms fatty acyl coA from of LCFA that donate FA to 2-MAG and DAG (catalyzed by acylcoA acyltransferases) to form TG
How is cholesterol processed in the cell?
acyl coA:cholesterol acyl transferase (ACAT) esterifies it to cholesteryl ester (takes FA from fatty acyl coA formed by fatty acyl coA synthetase from LCFA)
What is the outer layer of chylomicron made from? inner core?
outer layer- hydrophilic parts of phospholipids, cholesterol, apolipoproteins
core- cholesteryl ester, TG, fat soluble vitamins
Where are apolipoproteins made? What is the principal component of nascent chylomicrons?
intestinal mucosal cells, apoB48
What is the purpose of chylomicrons?
transport water insoluble TGs, lipids, cholesteryl esters, and vitamins through lymph and blood
How are chylomicrons cleared? What is produced?
lipoprotein lipases in capillary walls, breaks down TGs into glycerol and 3 FAs
What does the liver produce after de novo synthesis of fats?
VLDLs (with TGs packaged in them) released into blood
Which has a longer half life, VLDL or chylomicrons?
VLDL (still acted upon by lipoprotein lipase though)
What do apoproteins provide?
molecular recognition for enzyme reactions
When is ApoCII added to chylomicrons? What is it recognized by?
in maturation, recognized by lipoprotein lipase (activates it)
How does insulin affected lipoprotein lipase release?
increases it, increases the amount of hydrolysis of TGs and upatke of NEFA to be used as fuel in muscle or stored in adipocytes
