Class 6: Lipid Metabolism 2 Flashcards
What is the major source of carbon for FA synthesis?
Dietary carbohydrate
Where does FA synthesis primarily occur?
In the liver
Also occurs in brain, kidney, and adipose tissue
MAjor steps in FA synthesis:
- Formation of acetyl CoA
- Conversion of acetyl CoA to Malonyl CoA
- Elongation (addition of carbons)
- Desaturation (introduce of double bonds)
Citrate lyase
Lyses citrate to OAA and produces Acetyl CoA—supplies carbons for FA synthesis.
Malic enzyme
Converts malate to pyruvate
Citrate lyase and malic enzyme make up the:
Synthesis of acetyl CoA
What is the rate limiting step in FA biosynthesis?
Acetyl CoA carboxylase (ACC)
Acetyl CoA converted to Malonyl coa by carboxylation-adds CO2 (req’s biotin and ATP)
Regulation of ACC:
Allosteric:
+ Citrate
-long chain FA
Phosphorylation:
+ insulin
- epinephrine/glucagon
Induction:
+up-regulated w/ high carbohydrate diet
- down-regulated by high fat diet
2 carbon units from Malonyl CoA are sequentially added to growing fatty acyl chain to form palmitate.
Reacitons of FA synthesis occur on the:
Fatty acid synthase complex
2 identical dimers, each has 7 catalytic activities and an Acyl carrier protein (ACP),
FAS. Fatty acid synthase
ACP has a flexible arm w/ _____________________ group.
phosphopantetheine
Palmitate synthesis req’s:
8 acetyl CoA, 7 ATP, 14 NADPH,
Regulation of fatty acid synthase complex (FAS):
Allosteric:
(Presence of phosphorylated sugars)
Induction:
+high carb diet increases FAS synthesis
-high fat diet
Creating unsaturation stipulations:
Cant introduce double bonds beyond C-9…Cant synthesize linoleate and linolenate
That’s why theyre EFAs
Products generated by oxidation of 20 carbon FAs (arachidonic acid)
Eicosanoids
Serve as messenger and signaling molecules.
Serve as local hormones.
4 families: prostaglandins, prostacyclins, thromboxanes, and leukotrienes.
Aspirin blocks effects of:
Eicosanoids– prostaglandins
Mechanism 1 of phospholipid synthesis:
- Phosphatidic acid cleaved by phophatase to form DAG
- Head groups activated w/ CTP and become CDP-head grp which can react w/ DAG.
- After reaction, CMP is released and glycerophospholipid is formed
-phosphatidylcholine (PC) and phosphatidyethanolamine (PE)
Mechanism 2 of phospholipid synthesis:
- Phosphatidic acid reacts w/ CTP to form CDP-DAG.
- CDP-DAG reacts w/ head group, and releases CMP.
- Glycerophospholipid is formed
-phosphaidylinositol (PI) and cardiolipin
Most abundant sterol.
Component of membranes and precursor to vitamin D, bile salts, steroid hormones.
DAILY PRODUCTION: ~1 g, mostly in liver.
BIOSYNTHESIS REGULATED BY DIETARY INTAKE.
Cholesterol
Alicyclics compound.
27 C’s, 4 fused rings, 1 double bond btw C5 and C6, 2 CH3 at C18 and C19, 1 OH at C3, 8 member hydrocarbon chain attached to C17
Cholesterol.
Synthesis of cholesterol:
- Acetyl CoA is beginning molecule.
- It is reduced by HMG CoA Reductase(rate-limiting step-target of statins), which uses a NADPH.
- One step req’s ATP after and 3 req’ NADPH to form cholesterol.
The synthesis of __________ is a committed step in cholesterol formation.
Mevalonate
What is the rate limiting enzyme in cholesterol synthesis?
HMG CoA synthase
Reduced acetyl CoA to mevalonate
OH at C3 on cholesterol can become “cholesterol ester” by means of :
Acyl CoA acyl transferase (ACAT)
-extremely hydrophobic stored in lipid droplets(VLDL)
