BioChem: Lipid Biosynthesis
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- Where does fatty acid synthesis occur?
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-in the cytoplasm of most cells
*liver is major site - What are the three enzyme systems of fatty acid synthesis?
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1) biosynthesis of Palmitate from Acetyl-CoA
2) Chain elongation starting with palmitate
3) desaturation - List the intermediates for the biosynthesis of Plamitate.
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-acetyl-CoA to Acetyl-ACP to Acetyl synthase
-acetyl-CoA to malonyl-CoA to Malonyl-ACP
-both paths become Acetoacetyl-ACP, then B-3-Hydroxybutyryl-ACP then Crotonyl-ACP then Butytyl-ACP then Palmitoyl-ACP and lastly Palmitate - What are the starting and end materials for Palmitate synthesis?
- -Acetyl-CoA and Palmitate
- Once the two paths merge, what is the 1, 2, 3, and 4th things to happen in Fatty Acid Synthesis?
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-condensation
-first reduction
-dehydration
-second reduction
*further rounds of FA synthesis - What controls Fatty Acid Metabolism?
- -hormones such as Glucagon, epinephrine, and insulin
- What are the improtant control points?
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-release of fatty acids from adipocytes
-regulation of Carnitine Acyltransferase in the liver
-regulation of acetyl-CoA carboxylase - What does high insulin do after a meal?
- -inhibits breakdown of stored fats and stimulates the synthesis of malonyl-CoA
- What does malonyl-CoA inhibit?
- carnitine acyl transferase I so fatty acids are not oxidized
- When fasting, what happens?
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-insulin level drops releasing breakdown of fats
-epinephrine and glucagon increase -
What does the presence of citrate do to Acetyl-CoAcarboxylase?
What inhibits the active enzyme? -
-polymerizes it to a filamentous form of 4-8 million wt!
-polymer is active
-Palmitoyl-CoA - What are the shapes of elongation intermediates?
- -CoA esters
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What desaturates (forms double bond) Acyl-CoA molecules?
Where does desaturation of FA occur? -
-NADH and O2
-on the ER - What are the most common fatty acids in animal lipids?
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-oleic acid
-palmitoleic acid - What are Fatty Acyl Desaturates?
- -membrane bound flavoproteins which require Cytochrome B5 and O2
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What are essential fatty acids?
What can they be used for? -
-fatty acids that the body can't make (ex; mammals can't make double bonds beyond 9th carbon so linoleic acid can't be made)
-can be used to synthesize polyunsaturated fatty acids - How do you synthesize Arachidonic acid?
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-from linoleic acid
-Linoeoyl CoA to y-Linoeoyl CoA to Eicosatrienoyl CoA to Arachidonyl CoA
*all cis forms - What are isoprenoids called?
- -terpenoids
- What is the first step of terpenoid synthesis that occurs in all organisms?
- -Acteyl-CoA to Isopentenyl Pyrophosphate (IPP)
- What are the next 3 steps to synthesize Cholesterol?
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-IPP to Squalene
-Cyclization of Squalene
-Conversion of Lanesterol to Cholesterol - What are the steps to get from Actyl-CoA to IPP?
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-acetyl-CoA to Acetoacetyl-Coa
-to HMG-Coa
-to Mevalonic acid
-to Pyrophosphomevalonic acid -and finally to IPP - How does Squalene get to cholesterol?
- -squalene to Lanosterol which goes to cholesterol