lecture 26: PUFA Flashcards
arachidonic acid (ARA)
most prominent n6 from a functional standpoint
primary substrate for eicosanoid synthesis > pro-inflammatory
signal transduction role from release of phospholipase A2
PUFA (Polyunsaturated Fatty Acids)
hydrocarbon chains with 2 or more double bonds
PUFA classes in food and body
n-6 and n-3 classes, methyl carbon is the 1 carbon, n designates double bond location
linoleic acid
n-6 class, abundant in diet
𝛂-Linolenic acid
n-3, structuraly similar to linoleic acid
EPA, DHA
fish oil fatty acids
anti-inflammatory (n-3)
synthesis of 20 and 22C PUFAs by humans
elongation (from 18C), desaturation, B-oxidation
n-3 and n-6 cannot be interconverted
FA elongation (where does it occur, what happens)
occurs in the ER
elongase enzymes utilize n-6 and n-3 substrates and add carbons to CARBOXYL end
position of double bonds relative to methyl end remain the same
adds 2C at a time
desaturation of FAs
occurs in ER, delta 5 and 6 desaturases use n-3 and n-6
function of PUFA
1) lipid biomediators: regulators of inflammation, gene expression
2) membrane phospholipids: membrane functions
function of n-6 PUFA
ligands for PPARs > gene expression
linoleic acid and ARA have membrane structural effects
eicosanoids
synthesized from ARA, regulate many cellular functions
pro-or anti inflammatory signaling molecules
ratio based on n3/n6
process of eicosanoid synthesis
binding of a hormone/cytokine (TNFa) to a membrane bound receptor > phospholipase A2 cleaves ARA from membrane phospholipid
epoxygenase, COX or LOX pathway converts ARA to eicosanoid
prostaglandins
class of eicosanoids, produced by COX 1 or 2
pain, redness, swelling
induced by pro-inflammatory stimuli
COX enzymes are NSAID targets, active competitive inhibition
prostaglandin E2 (PGE2)
involved in pain, redness, swelling
EPA (eicosapentaenoic acid)
anti-inflammatory through competitive inhibition of ARA
compete for incorporation into plasma membrane > reduces ARA released by phospholipase A2
competes with ARA for metabolism > eicosanoids and resolvins
resolvins
derived from EPA
reduce pro-inflammatory cytokines
DHA
undergoes all three (elongation, desat, B-ox)
visual and cognitive functions
process in which DNA enhances visual function
1) rhodopsin undergoes CC upon light
2) surrounding phospholipids including DHA facilitate CC
3) DHA increases rate of coupling to transducin
DHA increases phosphodiesterase activity
3 transcription factors that bind lipids
PPARs, LXRs, SRBPs
PPAR and LXR can form heterodimers with RXR
Why can’t humans produce n-3 PUFA from an n-6 substrate?
position of the double bonds relative to the methyl remain the same
we don’t have desaturase enzymes (introduce double bond) beyond delta 9 carbon
in the process of converting linoleic acid (18:2) into arachidonic acid (20:4), two new double bonds have been introduced into the fatty acid. How is it that FADS1 and FADS2 can introduce double bonds at the ∆5 and ∆6 carbons, but the double bonds are not adjacent to each other?
carbons labelled relative to the carboxyl group
Elongase acts in between FADS1 and FADS2, two carbons are added to the carboxyl side which shifts the carbons’ numbered positions
elongation allows for saturated carbon in between, always adding 2
Which group of compounds play an important role in the pain-signaling pathway? Which PUFA is a substrate for this pathway? How do aspirin and ibuprofen work to decrease pain?
Prostaglandins are produced from arachidonic acid and COX enzymes, mediate pain and inflammation
NSAIDS are competitive inhibitors to COX enzymes, inhibiting prostaglandin synthesis > reduce pain, inflammation
Why is it important to maintain a healthy balance of omega-3 and omega-6 fatty acids? How is this balance reflected in eicosanoid production?
Omega-6: pro-inflammatory
eicosanoids (ARA)
Omega-3: produce anti-inflammatory compounds (EPA)
Competitive integration into membrane → both substrates to produce eicosanoids by COX enzymes, EPA also produces resolvins
Produce more of the inflammatory or anti-inflammatory eicosanoids based on n3/n6 ratio
