Unit 6 - Introduction to Lipids and their Metabolism Flashcards Preview

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Flashcards in Unit 6 - Introduction to Lipids and their Metabolism Deck (32):

what is the major form of metabolic energy in humans and where do we get it?

triacylglycerols (AKA triglycerides or TGs)
-obtained from animals and plants


what are the 3 reasons we store metabolic energy as fat?

1. carbons in triglycerides have lower oxidation state than carbons in CHO or PRO (9 kcal/g VS 4 kcal/g if dry, and 6x kcal if wet)
2. TG are stored in anhydrous state (no water), but CHO have twice their dry weight as bound water
3. fats don't participate in cell's osmotic balance (no bound water), so they can be stored to a larger fraction of cell volume


what is the "definition" of a fatty acid? what lengths are more abundant? what is the more common structure?

carboxylic acids with alkyl side chains (R-COOH)
-long chain C16 and C18 are more common
-hydrocarbon chains are saturated or unsaturated
--DB in polyunsaturated are almost always cis (separated by methylene group), and never adjacent or conjugated (or else too easily oxidized)


why are long chain FA rarely "free" for long?

ionized FA form micelles in aqueous solution, and are toxic to cells
-since toxic, non-esterified FA (NEFA) are bound to PRO via albumin (extracellular) or FA-binding PRO (intracellular)
-FA can also be esterified to compounds other than glycerol


what are the number of carbons and double bonds for
-arachidonic acids?

myristic: C14, 0 DB

palmitic: C16, 0 DB
palmitoleic: C16, 1 DB

stearic: C18, 0 DB
oleic: C18, 1 DB
linoleic: C18, 2 DB
linolenic: C18, 3 DB

arachidonic: C20, 4 DB


how are fats used as fuel? what organ cannot use it?

FA are derived from TG, and used by most tissues (heart, muscle, kidneys) as source of E
-FA-derived ACoA enters TCA to yield ATP and heat
-brain CANNOT use FFA as fuel b/c of BBB)


what are the 2 ultimate sources of NEFA?

1. diet (exogenous pathway)
2. synthesized de novo by liver and adipose (endogenous pathway)


what happens to excess FA?

from either exogenous or endogenous pathway, is stored as TG in adipocytes to be mobilized as NEFA when needed as fuel


what does bile contain?

bile acids/salts
phosphatidyl choline


what fats are more common in diets?

long chain TG (esterified to LCFA) are most common, and rarely MCT (esterified to MCFA)


what does digestion of FA involve?

hydrolysis of ester bonds in TG (catalyzed by TG-specific esterases = lipases)
-20% in lingual and gastric lipases (have acid pH optimum)
-the rest in SI via bile acids (digestive detergents)


what does pancreatic lipase enzyme activation require?? what does it cleave preferentially? what are its main products?

formation of a complex with colipase and a drop of emulsified lipid to stabilize "open" conformation and allow access to substrate
-partial hydrolysis of LCFA with preference for 1 and 3 positions
-main products are 2-monoacylglycerol (2-MAG) and NEFA


what happens to the products of lipid digestion?

absorption (passage into cells of intestinal mucosa)
-requires bile
-products first incorporated into mixed micelles that cross stationary aqueous boundary layer at intestinal wall
-then FFA, MAG, and glycerol diffuse/transport to intestinal mucosa cells


what are mixed micelles?

formed by bile acids, with nonpolar digestive products (2-MAG and NEFA) allowing translocation across stationary aqueous boundary layer at intestinal wall
-glycerol backbones are oriented toward aqueous phase


what is the major FA transporter in enterocytes? glycerol transport?

FATP5 (fatty acid transport protein 5) for FA
AQP3 (aquaborin family) for glycerol

absorption is predominantly carrier-mediated, but also can be passive via diffusion


what are the dual-roles of bile salts, and what happens to them after their job is complete?

function in both digestion and absorption
-remain in lumen and don't enter fat-absorbing enterocytes
-bile acids absorbed later on farther down intestine (enterohepatic recirculation)


what fats can be absorbed without prior enzymatic digestion?

-TG with SCFA or MCFA (breast milk, special diets) pass into intestinal cells w/o hydrolysis
-cholesterol, ADKE vitamins diffuse or are transported into intestinal cells


what happens if there are fatty acyl lipids that are not TG?

phospholipases and cholesteryl esterases in bile hydrolyze these


what are main causes of steatorrhea?

excessively fatty stools
1. failure of bile production or blockage of bile flow
2. exocrine pancreas dysfunction or obstruction of pancreatic duct
3. failure of uptake into intestinal mucosal cells (enterocytes)


what happens within intestinal mucosa cells (enterocytes)?

-resynthesis of TG from absorbed LCFA (bound to intestinal FA-binding PRO) and 2-MAGs
--Acyl-CoA synthetase (thiokinase) catalyzes formation of acyl-CoA derivatives of LCFA
--acyltransferases (transacylases) transfer 2 LCFA to 2-MAG (to 1,3 positions) to make TAG


for LCFA...
-chain length
-present in diet?
-primary site of absorption
-does it need pancreatic lipase?
-does it need micelle formation?
-is it in feces?

-over 12 C long
-present in large amounts as TGs
-absorbed mainly in SI
-needs pancreatic lipase and micelle formation
-minimally in feces


for MCFA...
-chain length
-present in diet?
-primary site of absorption
-does it need pancreatic lipase?
-does it need micelle formation?
-is it in feces?

-from 8 to 12 C long
-in small amounts as TGs in diet
-absorbed mainly in SI
-doesn't need pancreatic lipase or micelle formation
-not in feces


for SCFA...
-chain length
-present in diet?
-primary site of absorption
-does it need pancreatic lipase?
-does it need micelle formation?
-is it in feces?

-less than 8 C long
-not in diet, but bacterial conversion of nonabsorbed CHO
-absorbed mainly in colon
-doesn't need pancreatic lipase or micelle formation
-substantially present in feces


does thiokinase act on SCFA, MCFA, and/or LCFAs?

it only acts on LCFAs
-doesn't convert SCFA or MCFA to corresponding thioesters, and aren't incorporated into resynthesized TG


how are materials packaged in nascent chylomicrons

inside/hydrophobic: TAGs, cholesteryl ester, fat soluble vitamins

outside/amphipathic/hydrophilic: phospholipids, cholesterol, apolipoprotein B-48


what is apo-B48?

principal protein component of nascent chylomicrons when produced in intestinal mucosa
-other proteins are added later in the bloodstream as chylomicrons undergo restructuring and maturation


what enzyme clears chylomicrons, and how long is clearance?

lipoprotein lipase does the clearance (delipidation) that takes about 10 minutes (equals half life of chylomicron)


how are chylomicrons cleared?

lipoprotein lipase in capillary endothelial walls of various tissues (especially muscle and adipose)
-cleaves all 3 ester bonds to make glycerol and NEFA
-apoproteins supply selectivity for molecular recognition, especially CII


why is serum a few hours after a fatty meal often milky?

high concentration of chylomicrons


what does hepatic lipase do?

delipidates VLDL (higher ratio of protein to lipid, and more cholesterol) to make LDL


what effect does insulin have on lipoprotein lipase release?

promotes release from adipocytes and muscle


what is colipase?

cofactor for pancreatic lipase
-secreted as inactive precursor by pancreas, and activated in duodenum thru action of trypsin