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Lipids- synthesis, degradation
All about lipid
37
Other
Undergraduate 3
02/11/2009

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Term
Key regulated step in FA synthesis
Definition
Production of Malonyl-CoA by acetyl-CoA Carboxylase
Term
Steps of Beta oxidation of saturated FA
Definition
1. Fatty-Acy-CoA  + Dehydrogenase + FAD 
   -> Enoyl-CoA (α-β double bond) + FADH2 
2. Enoyl-CoA + Hydratase + H2O
   -> L-β-hydroxyacl-CoA
3. L-β-hydroxyacl-CoA + Dehydrogenase + NAD
   -> β-ketoacyl-CoA + NADH2 
4. β-ketoacyl-CoA + Thiolase + CoA 
   -> A-CoA + FattyAcyl-CoA (2 c shorter)
Term
Chylomicrons
Definition

-Formed in intestinal mucosa

-TAGs, cholesterol &apolipoproteins

-Move through lymph 

-Mono layer of lipids w/ hydrophobic core 

Term
apoCII
Definition

activates lipoprotein lipase

 

 

Term
Lipoprotein Lipase
Definition
Converts TAGs into FAs and Glycerol 
Term
Digestion/ Absorption of fats
Definition
1. Bile salts imsulfy
2. Intestinal lipases degrade to MAGs and FFAs
3. MAGs and FFAs taken up by intestinal mucosa -> TAGs
4. TAGs incorporated into chylomicrons, move thru lymph
5. apoC-II activates lipoprotein lipase
6. lipoprotein lipase converts TAGs to FAs and glycerol
7. FAs enter cells where they are oxidized/ reabsorbed
 
Term
What stimulates transport of FAs?
Definition
Glucagon/ Epinephrine
Term
Fatty Acid Activation for synthesis
Definition
1. Fatty-Acyl Co-A synthase + ATP + FA 
   -> PPi + Fatty Acyl- AMP
2. Fatty Acyl- AMP +CoA
   -> Fatty Acyl- CoA 
 
*Driven by cleavage of ATP --> PPi --> 2Pi 
Term
Carntine Acyltransferase I
Definition
-Transports Acyl group from cytosolic fatty-acyl-CoA to carnitine 
-Inhibited by Malonyl-CoA 
Term
Carnitine/ Acyl-carnitine transporter
Definition
Antiporter that shuttles acyl-carnitine into mitochondria and carnitine out. 
 
 
 
Term
Describe electron transfer in the acyl-CoA dehydrogenase step of beta oxidation
Definition
e- from both alpha and beta carbons are transferred to FAD (to form FADH2) 
Term
What cofactor is necessary for the thiolase activity of beta oxidation?
Definition
CoA
Term

T/F

Beta oxidation requires a cis double bond 

Definition
False- it requires trans double bonds at alpha-beta position
Term
Rules for desaturating fatty acids
Definition
1. Double bonds must be introduced 3 C apart
2. Can't introduce doub bonds past C9
3. Can only introduce double bonds at C4, 5,6 and 9
 
*Note elongation occurs 2C at a time 
 
Term
Activation/ Inhibitor of ACC
Definition

1. INACTIVATE

low blood sugar -> Glucagon -> PKA

Glucagon: DEpolymerizes and phosphorylates 

Palmitoyl-CoA/ Malonyl-CoA 

 

2. ACTIVATE

High blood sugar-> insulin-> phosphatase

insulin: polymerizes/DE-phosphorylates 

Citrate/ A-CoA 

 

 

Term
Fatty Acid Desaturases/ Mixed function oxidase
Definition
*O2 is terminal e- acceptor
* NADPH is electron donor 
 
-Add double bonds and O2 + 2H+ -> H2O 
 
-Req 4e- (2 from NADPH, 2 from Fatty Acyl)
 
Term
Cyt P450 enzymes
Definition
Detoxicify liver , cholesterol synthesis, meds
 
NADPH donates e- 
RH +O2 -> ROH + H2O 
Term
Beta-Oxidation of unsaturated
Definition
-Only "sees" first 3 C
1.Cis bond at β-γ position + ΔΔ enoyl-CoA isomerase 
   -> Trans d.b. at α-β position 
2. Beta-ox starting at enoyl hydratase and ending
   after acyl-CoA dehydrogenase 
   -left w/ 2-3 db and 4-5 db
3. 2,4 dienoyl reductase uses NADPH to add 2e-
   ->  3,4 double bond (trans)
4. Isomerase moves bond to α-β and Beta-ox
   continues as normal 
Term
Thiolase activities
Definition
-Can cleave ketoacyl (beta-oxidation)
-Can form double (ketone body metabolism)
Term
β- hydroxybutyrate
Definition

1. Formed from acetoacetate by dehydrogenation 

    -Uses NADH + H 

2. Transported to tissue in starvation states

3. Leads to ketoacidosis 

 

Term
Beta-ketoacyl-CoA transferase
Definition
-NOT found in liver
- Uses succinyl-CoA and acetoacetate to form A-CoA 
Term
Mobilization of fat from adipose tissue
Definition
1. Glucagon/ epi stimulate AC-> cAMP->PKA
2. PKA phosphorlyates HSL and perilipins
3. Perilipins change conformation allow HSL access to TAGs 
4. HSL +TAGs -> FFAs 
5. FFAs bind w/ serum albumin and are transported where they need to go
Term

Coenzyme B12

Definition
-Used in conversion of propionyl-CoA to succinyl-CoA
 
-Is a cofactor for methylmalonyl-CoA mutase
Term
Steps of propionyl-CoA to succinyl-CoA conversion
Definition
1. Propiony-CoA + HCO3- + ATP + biotin +carboxylase
   -> D-methylmalonyl-CoA + ADP
2.  D-methylmalonyl-CoA +epimerase
    -> L-methylmalonyl-CoA
3. L-methylmalonyl-CoA +methylmalonyl-CoA mutase + biotin
   -> Succinyl-CoA 
Term
ACP
Definition
Immobile carrier protein for substrates in FA synthesis
within complex
 
-Associates w/ fatty acid synthase 
Term
Steps of fatty acid synthesis
Definition
Enzyme for all = FA synthase w/ ACP attached
 
1. "Charging"of FAS/ACP w/ acety-CoA
    *acetate stays, CoA is released
2. "Charging" of FAS/ACP with malonyl-CoA to ACP
    *CoA released 
3. KS-> condensation (CO2 loss) and  add'n of
    acetate to new end of "malonyl"
4. KR-> Reduction of β-keto group (using NADPH)
5. HD -> Dehydration of β-hydroxy group
6. ER -> Reduction of β doub bond (using NADPH)
7. KS -> translocation of FA to Cys on ACP 
8. Repeat starting at step 2 
Term
Where does phospholipase D cleave?
Definition
Between the phosphate and the head group of  a phospholipid
Term
Where does phospholipase C cleave?
Definition
Between the glycerol and the phosphate of a phospholipid
Term
In elution chromotrography, what order to substances elute?
Definition
1st= non-polar, uncharged
2nd=non-polar, charged
3rd= polar/ charged 
Term

1. How do beta-barrels look on hydrophobicity plots?

2. How do alpha helices look on hydrophobicity plots?

 

Definition
1. Bet-barrels have no real shape (lots of zig-zags, mostly below the line but with some above it)
 
2. Alpha helical segments over 20 residues are above the mid line of a plot  
Term
Storage fats
Definition
TAGs
-store way more than glycogen by wet weight
-Stores could last way longer than glycogen 
Term
Membrane Lipids
Definition
1. Phospholipids
    -glycerophospholipds and some sphingolipids
 
2. Glycolipids
   -Some sphingolipids, galactolipids
Term
Glycerophospholipids
Definition
Phosphatidic acid: glycerol3-P-H
 
Phosphatidylcholine: (CH2CH2N(CH3)3) 
 
Phosphatidylserine: P-CH2CH-NH3; OH on C2 
 
Phosphatidylglycerol: P-C3 w/ OH on C2, C3
 
PIP2: has inostitol 4,5bisphosphate (hexagonal) 
 
Cardiolipin: P-Phosphotidylglycerol 
 
 
 
Term

Galactolipids

Definition
Have sugar attached to C3
Term
Sphingolipids
Definition
*Amide bond on C2, transbond in "tail" and OH on C1
 C3 has O linked to functional group
Ceramide-  O-H
Nuetral glycolipids/ glucocerebrosides: 1 sugar
Globosides: 2-4 sugars 
Ganglioside:4-6 sugars 
 
*Used in myelin/ insulation and in blood type recognition 
Term
Prostaglandins
Definition
-Ecosanoid fatty acid derivative
-Produced by COX 1 and 2 
Term
COX inhibition
Definition
-Inhibited by NSAIDS 
-Inhibition of COX 1 leads to problems w/ stomach
-Inibition of COX 2 (cause of pain/swelling) leads to problems w/ heart 
 
*Celebrex, vioxx target mostly COX-2 
 
 
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