Intro to Lipids and their Metabolism Flashcards

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
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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
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3
Q

why store metabolic energy as fat?

A
  1. 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
  2. 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
  3. fats don’t participate in the cells osmotic balance so they can be stored as a large fraction of the cell volume
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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
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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
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6
Q

myristic

A

-14 C, no DB

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7
Q

palmitic

A

-16 C

no DB

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8
Q

palmitoleic

A
  • 16 C

- 1 DB

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9
Q

stearic

A
  • 18 C

- 0 DB

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10
Q

oleic

A

18 C

1 DB

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11
Q

linoleic

A

18 C

2 DB

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12
Q

linolenic

A

18 C

3 DB

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13
Q

arachidonic

A

20 C

4 DB

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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
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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
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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
Q

fat as fuel 2

A
  • 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
Q

chylomicron clearacen

A
  • lipoprotein restructing involves protein and lipid components
  • apoproteins provide selectivity with molecular recognition
27
Q

lipoprotein lipase

A
  • 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
Q

liver cells

A
  • FA to glycerol esters and then package TG in VLDL particles released into plasma
  • lipoprotein lipase releases
29
Q

hepatic lipase

A
  • major role in delipidation of VLCL

- makes higher ratio of protein to lipid