Lipid Metabolism pt. 2 Flashcards
What are the sites of lipid synthesis?
-all tissues synthesize lipids
-qualitatively major sites:
-liver
-adipose tissue
-mammary gland (lactating)
Explain the major site in humans; the liver.
-triacylglycerol synthesized from glucose (and fructose)
-most triacylglycerol comes from the diet
-TG synthesized when:
very low fat diet or very high carbohydrate diet
-released by liver as VLDL
-taken up by adipose tissue- lipoprotein lipase
Review B-oxidation
-takes place in mitochondria
-two carbon “units” removed as acetyl-CoA from fatty acyl-CoA
-Acetyl-CoA oxidized
-forms NADH and FADH2
Is lipid synthesis an opposite of B-oxidation?
No!
What are the similarities between FA synthesis and B-oxidation?
-built by addition of 2-carbon units to growing fatty acids
-similar intermediates are formed
What are the differences between FA synthesis and B-oxidation?
-FA synthesis is in the cytoplasm
-acetyl-CoA gets out of the mitochondria:
condenses with OAA to form citrate (citrate synthase reaction), then transported out (tricarboxylate carrier) and then is cleaved by citrate lyase
-involves malonyl-CoA, which is a three carbon intermediate not involved in fatty acid oxidation
What is acetyl-coA carboxylase?
1st step in fatty acid synthesis from cytoplasmic acetyl-CoA, adds one carbon onto acetyl coA at the expense of 1 ATP to make malonyl-coA
What are the two steps of fatty acid synthesis:
7 acetyl-CoA + 7ATP + 7CO2 –> 7 Malonyl-CoA + 7ADP + 7Pi (acetyl-CoA carboxylase)
then:
Acetyl-CoA + 7 malonyl-CoA + 14 NADPH (from PPP) + 14H+ –> palmitate + 7CO2 + 8CoA + 14NADP+ 6H2O
(fatty acid synthase complex)
Explain fatty acid synthase,
acyl carrier protein
and use of NADPH
-enzymes of FA synthesis in the form of a multi-enzyme complex
-intermediates are link to them, a component of fatty acid synthase
-the electron donor (oxidation uses NAD+ and FAD as electron acceptors)
What is the structure of fatty acid synthase?
-dimer of two 240 kDa proteins (huge)
-function independently
-each consists of 7 enzyme activities and ACP
Overview of Fatty acid synthesis.
Starts with 1 acetyl-CoA and malonyl-CoA, releases CO2, double bonds are reduced using NADPH
Gets released once you reach 16 carbons
How is acetyl-CoA carboxylase regulated?
-allosteric regulator- citrate
-regulation by : phosphorylation/dephosphorylation
phosphorylated (inactivated) by glucagon, AMPK
dephosphorylated (activated) by insulin (this from polymerizes)
How is acetyl-CoA allosterically regulated by citrate?
-dephosphorylated from highly activated with no citrate
-citrate partly overcomes inhibition due to phosphorylation, which will decrease the activity
What are the 3 products of eicosanoid synthesis?
-prostaglandins
-thromboxanes
-leukotrienes
Explain the actions of anti-inflammatories.
NSAIDS:
-inhibit cyclooxyrgenase
-aspirin covalently, all others are reversible
-decrease prostaglandins and thromboxanes
Steroids (glucocorticoids):
-decrease expression of PLA2 and COX
-decrease leukotrienes
What are the 3 precursors for triacylglycerol and phospholipids?
-glycerol 3-phosphate
- fatty acyl-CoA
Phospholipid needs headgroup (serine choline, etholamine)
What is a triacylglycerol?
three fatty acids esterfied to a glycerol backbone
What is a triacylglycerol?
three fatty acids esterifed to a glycerol backbone
What are the two sources of glycerol-3-phosphate?
glycolysis: glycerol 3-phosphate dehydrogenase
glycerol: glycerol kinase
How is fatty acyl-CoA formed?
fatty acid + CoASH + ATP –> fatty acyl-CoA + AMP + Phi (fatty acyl-CoA synthetase)
How is phosphatidic acid synthesized?
glycerol 3-phosphate + 2 fatty acyl-CoAs –> diacylglycerol 3- phosphate + 2 CoASHs
-diacylglycerol 3-phophate is more commonly called phosphatidic acid
Explain phosphatidic acid in lipid synthesis.
Phosphatidic acid:
Attachment of head groups make phospholipids
Phosphatidic acid phosphatase removes a phosphate group, creating diacylglycerol, with acyl transferase and another fatty acyl-CoA can become a triacylglycerol
Go over cholesterol synthesis mechanism in notes
done
What is a statin?
inhibit HMG-CoA reductase, prevent heart attacks and lower cholesterol
What is progesterone synthesis?
-precursor for all steroids
-cholesterol is a precursor for steroid synthesis and bile acid synthesis
What is cholestyramine and how does it work?
-first drug shown to lower cholesterol
-binds to bile acids
-increases bile acid excretion
-increases conversion of cholesterol to bile acids which lowers the amount of circulating cholesterol
