What can plants do that humans can't in regards to PUFAs? What can mammalsdo with PUFAs? What's special about these PUFAs?
Only plants can synthesize PUFAs (polyunsat FAs) with w-3/w-6 double bonds.
Mammals can elongate and desaturate (convert 18:2 w-6 linoleic acid to 20:4 w-6 arachidonic acid).
What two specific FAs are made from linolenic acid? Where are these FAs processed? What is it essential for? (2) What type of lipid is it incorporated into? and what organs? (2)
DHA (dacosahexaenoic acid) and EPA (eicosapentaenoic acid). 22:6 and 20:5
Processed in livers. Essential for normal vision and cognition.
Incorporated into phospholipids in retina and brain.
Who is deficient in desaturases and elongation enzymes in liver? 2 How do they get DHA and EPA then?
Fetuses and newborns
From breast milk
Name steps in synthesis of prostaglandins, thromboxanes, and leukotrienes. 3
1. Signal from cytokine (via plasma membrane receptor linked to G protein) activates phospholipase A2
2. PLA2 hydrolyzes FAs at sn2 position, especially 20:4w6 (arachidonate)
3. Arachidonate can turn into prostaglandins/thromboxanes via cyclooxygenase (COX) or leukotrienes via lipooxygenase (LOX).
What does COX do and what does it stand for? LOX? What inhibits PLA2? What inhibits COX? (3)
COX = cyclooxygenase: arachidonate --> prostaglandins and thromboxanes. Inhibited by aspirin, NSAIDS (ibuprofen), COX2 inhibitors.
PLA2 is inhibited by corticosteroids.
How do steroids inhibit inflammation?
By inhibiting PLA2 (which is responsible for cleaving arachidonate (precursor of inflammatory molecules) from phospholipids.
How do eicosanoids made from w3 PUFA (20:5 and 22:6) protect against effects of thromboxanes (from 20:4)? (4)
1. Compete with 20:4w6 for release by PLA2
2. Compete with 20:4w6 for COX so fewer w6 metabolites synthesized.
3. Different effects: Thromboxane 3 is weaker than thromboxane 2 (w6) for platelet aggregation. ALSO prostaglandin 2 and 3 are equal inhibitors of aggregation, so balance is shifted towards anti-aggregation.
Basically, weakens platelet aggregation and shifts balance towards anti-aggregation.
What is the proposed mechanism by which low dose aspirin prevents a heart attack?
inhibits COX, inhibiting synthesis of prostaglandins and thromboxanes that are proinflammatory
What is proposed mech for protective effects of fish oils?
How would you determine whether premature babies are currently getting enough w3 FAs in diets? What info would you use?
If supplementation seems necessary, how would you decide how much w3-FA to give to premature babies?
Measure blood levels. Measure w6 vs w3 should be 1:1
What does a high ratio of w6:w3 lead to? (4) what else in babies? (2)
Inflammation, blood clotting, EPA def (skin rash) and w3 FA def in babies.
Impaired cognition and vision.
What is the C:n thing for DHA? EPA? Full name?
What is the C:n thing for their precursor and full name? What is the order of precursors? 3
DHA = Dacosahexaenoic acid 22:6
EPA = eicosapentaeoic acid 20:5
a-linolenic acid 18:3w3
ALA --> EPA --> DHA
What are all eicosanoids derived from? Cleaved from what lipid at what position?
Essential fatty acids (arachidonate or EPA - eicosapentaenoic acid), located at SN2 position of a phospholipid
Describe pathway for eicosanoid synthesis and draw.
What are the 3 enzymes important in this pathway?
1. Inflammation: a cytokine via receptor/G protein activates phospholipase A2
2. PLA2 hydrolyzes FA at SN2 position, particularly arachidonate.
3. 20:4 is converted into biologically active molecules called eicosanoids via COX and LOX (lipooxygenase --> leukotrienes; cyclooxygenase --> thromboxanes and prostaglandins).
What compounds/drugs inhibit eicosanoid formation? By acting on which enzymes?
PLA2 is inhibited by corticosteroids
COX is inhibited by aspirin, NSAIDS (i.e. ibuprofen), and COX 2 inhibitors.
What is the main difference between COX 1 and 2? How are they activated? Name 3 ways
COX 1 is constuitively on
COX 2 is nonconstiutively on and is activated by cytokines, growth factors, tumor promotors, etc
How can eicosanoids made from w3 FAs protect against effects of thromboxanes? (4 ways)
Also, what is C:n of thromboxane in question?
1. Compete with 20:4w6 for release by PLA2
2. Compete with 20:4w6 for COX so fewer w6 metabolites are synthesized.
3. Different effects: (1) Thromboxane 3 (from w3s) is weaker than thromboxane 2 (from w6s) for platelet aggregation (2) Prostaglandin 3 and prostaglandin 2 BOTH inhibit aggregation, so will tip balance towards anti-aggregation.
In which tissues are lipid droplets found? In greatest density? What in cell are lipid droplets close to in muscle cells?
In nearly all tissues. Greatest density in adipose tissue
Lipid droplets in myocytes are closest to mitochondria to provide FAs for energy.
When are TAGs generally synthesized? What type of diet?(3) What happens if no fat is in diet?
When FA intake is greater than needed for biosynthesis of membranes, etc.
High calorie/carb/fat diet.
If no fat in diet, body will undergo de novo synthesis of FAs.
What are the basic steps to synthesizing TAG? 3 steps. Name according enzymes 1-2; 2-1; 3-3
1. Generating glycerol 3 P (glycerol kinase, glycerol3P DH)
2. Activating FAs via acyl coa synthetase
3. Attaching FAs to glycerol backbone via GPAT, MGAT or DGAT (pretty much the same things)
What are substrates for TAG synthesis?
Glycerol 3 phosphate and 3 long chain fatty acyl CoAs.
Where is glycerol3P synthesized? what are the main differences between these organs? (3)
Liver and adipose tissue.
Liver has glycerol kinase, can use ATP or NADH vs. only NADH, and has GLUT 2 transporters rather than GLUT 4 transporters (non-insulin dependent).
What is generally the precursor to glycerol 3 P? Where does this precursor come from? What is the enzyme that transforms precursor to glycerol 3 P? What does this enzyme require?