Intro to Lipids and their Metabolism Flashcards
(29 cards)
1
Q
lipids in health and disease
A
- crucial for understanding major health problems
- CAD, stroke, obesity, diabetes, cancer
- key to metabolic integration
- key targets of drug discovery
2
Q
triglycerides
A
- major storage form of metabolic energy
- three carbon center with three FA attached
- glycerol plus FA- glycerol has OHs and is slightly water soluble
3
Q
why store metabolic energy as fat?
A
- carbons in triglycerides have a lower oxidation state than carbons in carbs or protein, more than twice the energy per dry weight- 9kcal/g compared to 4
- TG are stored in anhydrous state, whereas carbs have twice their dry weight as bound water- fat has 6x the metabolic energy per gram of wet weight tissue
- fats don’t participate in the cells osmotic balance so they can be stored as a large fraction of the cell volume
4
Q
FA
A
- carboxylic acids with alkyl side chains- R-COOH
- chain lengths found most abundantly in TG and other lipids are 16 and 18.
- short-2 to 4
- med 6-10
- long-12-26
- long chain most abundant
- saturated or unsaturated
- DB in polyunsaturated are neither adjacent or conjugated
- naturally occurring DB are cis
- ionized long chain FA form micelles that are toxic to cells
- long chain FA are either esterified or tightly bound to proteins
- saturated very flexible, fully extended form energetically favored, cis adds 30 degree rigidity, lower melting temp
- need unsat to keep membranes fluid and TG in liquid form
5
Q
FA 2
A
- derived from TG and used as fuel
- free FA ^ non-esterified FA
- brain can’t use them
- two sources-diet via exogenous pathway
- and FA synthesized de novo via endogenous pathway
- excess FA stores as TG in adipocytes to be mobilized when needed
6
Q
myristic
A
-14 C, no DB
7
Q
palmitic
A
-16 C
no DB
8
Q
palmitoleic
A
- 16 C
- 1 DB
9
Q
stearic
A
- 18 C
- 0 DB
10
Q
oleic
A
18 C
1 DB
11
Q
linoleic
A
18 C
2 DB
12
Q
linolenic
A
18 C
3 DB
13
Q
arachidonic
A
20 C
4 DB
14
Q
fat as fuel
A
free FA released from TG are used by most tissues as a source of energy
- FA derived acetyl CoA enters TCA, yielding ATP and heat
- brain cannot use free FA as fuel because BBB prevents transport
- FA can be obtained from diet or synthesized
- excess converted to TG for storage
15
Q
when we eat fat
A
- digested
- absorbed in intestinal mucosal cell where it is
- resynthesized, packaged into lipoproteins
- exported to use as fuel or storage
16
Q
digestion of triglycerides
A
- bile acts as a detergent
- bile needed for lipid dispersion (emulsification)
- not just TG, other lipids, including fat soluble vitamins-ADKE
- bile contains bile acids, phosphatidyl choline, cholesterol
- hydrolysis of ester bonds in TG-catalyzed by lipases
- long chain insoluble in water and emulsified before digestion can occur
- chewing and stomach contractions produce finely dispersed droplets
- lingual and gastric lipases, then bile acids
17
Q
pancreatic lipase
A
- enzyme activation requires formation of a complex with colipase and a droplet of emulsified lipid, stabilizing the open conformation and allowing access to substrate
- enzyme is an esterase, cleaving preferentially at 1 and position
- releases monoacyl glyceride (MAG) and FA
- small intestine-duodenum and proximal jejunum
- at water lipid interfaces
18
Q
products of lipid digestion
A
- absorbed into cells of intestinal mucosa- also requires bile for mixed micelles
- incorporated into mixed micelles that cross the stationary aq boundary layer at intestinal wall
- glycerol backbones pointed toward aq phase
- free FA, MAG and glycerol diffuse or are transported by carrier proteins into intestinal mucosa
- bile salts remain in lumen and do not enter fat absorbing enterocytes
19
Q
some fats don’t need digestion
A
- TG with short and medium chain FA in breast milk and some special diets pass into intestinal cells without hydrolysis
- cholesterol, ADKE vitamins also diffuse or are transported into intestinal cells
- food contains fatty acyl lipids besides TG
- other enzymes in the intestinal lumen hydrolyze FA from phospholipases and cholesteryl esterase
20
Q
causes of steatorrhea
A
- failure of bile production or blockage of bile flow
- exocrine pancreas dysfunction or obstruction of pancreatic duct
- failure of uptake into intestinal mucosal cells
21
Q
synthesis of TG and assembly into nascent chylos
A
- fat soluble vitamins to chylo
- MAG to triacylglycerol via two processes that release CoA (acyltransferases)
- long chain FA to FA CoA using ATP, then into tryacyl glycerides to chylo (acyl CoA synthetase)
- cholesterol directly in or to cholesteryl ester and then in
- chylo then goes to lymphatic system
- they are amphipathic
- amino acids give apolipoproteins
- then pick up more from HDLs
22
Q
LCFA
A
- chain length over 12
- large amt in diet
- origin in diet as TG
- primary site of absorption in SI
- needs pancreatic lipase and micelles, minimal presence in feces
23
Q
MCFA
A
- 8-12
- in small amts in diet
- in diet as TG
- small intestine
- doesn’t req lipase or micelles and not in feces
24
Q
SCFA
A
less than 8
- in small amts in diet- vinegar
- bacterial converstion of non-absorbed CHO in colon
- doesn’t need pan lipase or micelles
- substantial amt in feces
25
fat as fuel 2
- TG produced in intestinal cells must be transported through the lymph and blood to tissues that use TG as source of fuel
- packaged into chylomicrons-lipoprotein particle
- apo-B48 is principle component of nascent chylos
- chylos transport other lipids too
- most hydrophobic on the inside
26
chylomicron clearacen
- lipoprotein restructing involves protein and lipid components
- apoproteins provide selectivity with molecular recognition
27
lipoprotein lipase
- in cap endo wall of various tissues
- cleaves all 3 ester bonds-glycerol and NEFA are products
- cleared rapidly from blood, half life of 10 min
- serum obtained a few hours after a fatty meal is often milky with chylos
- NEFA can also come from adipocytes
28
liver cells
- FA to glycerol esters and then package TG in VLDL particles released into plasma
- lipoprotein lipase releases
29
hepatic lipase
- major role in delipidation of VLCL
| - makes higher ratio of protein to lipid
