The majority of carbons that contribute to FA synthesis come from where?
-carbohydrates that are ingested, and undergo the first few steps of glycolysis. Specifically form DHAP or G3P
Where is FA synthesis most common in occurring?
brain, liver, kidneys and are stored in adipocytes
In the cells where does FA synthesis occur?
cytoplasm
What are the starting units and the addition units of FA synthesis?
- starts with acetyl CoA
- Malonyl CoA contributes 2 C additions to the growing FA chain
What is the primary electron carrier that is used?
NADP+—–> NADPH
What is the committed/rate limiting step in FA synthesis?
conversion of Acetyl CoA to Malonyl CoA via acetyl CoA carboxylase
What are the 3 steps in FA synthesis?
Conversion of Acetyl CoA to Malonyl CoA
- Elongation
- Desaturation
The elongation step of FA synthesis is what?
-malonyl CoA donates 2 C’s to the growing FA chain
What is the point of a desaturation reaction with FA synthesis?
this process allows for the addition of double bonds to the chain
What is the coenzyme for carboxylases?
-biotin
After the TCA cycle, citrate is produced and can be used to produce what components?
- supply C’s for FA synthesis
- use of citrate lyase to from Acetyl CoA
What enzyme is used to convert Acetyl CoA to Malonyl CoA?
acetyl CoA carboxylase (ACC)
What factors with increase or promote the activity of ACC?
- citrate
- insulin
- high carb/low fat diet
- available amount of B7—> biotin (which is cofactor for carboxylases)
What factors with inhibit the activity of ACC?
- [Long chain FA]
- epinephrine/glucagon (signal energy burning)
- low carb/ high fat diet
- deficiency of Vit. B7
What ways is the ACC regulated?
- phosphorylation pathways
- allosteric pathways
- gene expression pathways
Fatty acid synthase is the enzyme where FA synthesis occurs. What is the structural components that allow this?
- 2 monomers that form a dimer
- each monomer has 7 catalytic activities and acyl carrier proteins
- the acyl carrier protein contains a phosphopantetheine group that binds with the other monomers cysteinyl sulfhydryl group. (thioester bond)
What are the four stages of the FA synthesis process?
- condensation: loss of ACP, and CO2
- reduction: NADPH—> NADP+
- dehydration: loss of water
- reduction: NADPH—> NADP+
What three enzymes are used in the desaturation of FA in order, and what is the final product?
- NADH cytochrome b5 reductase
- cytochrome b5
- stearoyl CoA desaturase: produces oleoyl CoA and water
What are the two main components required for TAG synthesis?
TAGs can form from glycerol or glucose. The main intermediate is G-3-P
What are the steps to forming TAGs?
G-3-P converts to phosphatidic acid; converts to diacylglycerol; converts to TAG and combine with apoproteins to move to the liver as very low density lipoproteins
What is needed to form eicosanoids?
phospholipids and diacylglycerols
What are the types of eicosanoids that exist?
- leukotriene (B4)
- prostacyclin (PGI2): vasodilator
- thromboxane A2: vasoconstrictor
- prostaglandin (E2)
Lipoxygenases form what type of eicosanoids?
-leukotrienes
Prostaglandin synthase forms what type of eicosanoids?
- prostaglandin
- prostacyclin
- thromboxane
What are the products of phosphatidic acid in the mechanism 1?
- phosphatidylcholine
- phosphatidylethanolamine
What products form from mechanism 2 from phosphatidic aicd?
- phosphatidylinositol
- cardiolipin: major component of mito. matrix
What is the main difference between mechanism 1 and 2 in the phospholipid synthesis?
the main difference is where the CDP head group attaches to the diacylglycerol.
- mech 1: adds CDP-head group in one step
- mech 2: adds CDP and then adds the head group.
What component is the primary “hub” for forming phosphatidylserine/choline?
- PE is swapped to PS
- PE if methylated forms PC
Cholesterol is derived from what?
Acetyl CoA and Acetoacetyl CoA
What is the rate limiting/control step of cholesterol production?
- HMG CoA Reductase
- -converts acetyl CoA to mevalonate.
- -produces 2 NADP+ and CoA
Where do statins work primarily to reduce the level of cholesterol?
-at HMG CoA reductase, the rate limiting step
What happens during fasting after mevalonate is formed? There is a second compound produced, what is it and what will it do?
- acetyl CoA and acetoacetate
- -instarvation acetyl CoA forms ketone bodies
Stage 2 of cholesterol synthesis is how many steps, and how many C’s from start to finish?
- occurs in three reactions and start with 5–>10–>15–>20 C’s
- squalene is able to begin the ring cyclization of cholesterol.
What is the name of the enzyme that helps stabilize the structure for ring formation?
-oxidosqualene cyclase, maintains the ring structure of the intermediates until stabile cholesterol is formed
The accumulation of cholesterol is what?
LDL that allows release into blood stream and delivers cholesterol to the liver and peripheral tissue
HDL is able to transfer APoE and APoCII to what molecules?
- chylomicrons
- VLDL
- IDL
- LDL
If a person has a cholesterol ester transfer protein mutation or deficiency what is the ultimate problem?
-TAG and phospholipids are not able to transfer from LDL, VLDL, IDL to HDL.