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major source of carbon for fatty acid synthesis |
dietary carbohydrates |
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Fatty acid synthesis |
occurs primarily in the liver also occurs in brain, kidneys, adipose tissue components are located in cytoplasm: |
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citrate |
supplies the carbons for fatty acid synthesis |
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Levels of mitochondrial acetyl CoA regulate its own synthesis |
inhibits pyruvate dehydrogenase if there is too much acetyl CoA stimulates pyruvate carboxylase if need to make more Acetyl CoA bc that makes oxaloacetate into citrate, and citrate provides carbons for FA synthesis |
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Regulation by INSULIN |
stimulates pyruvate dehydrogenase activity to upregulate synthesis of cytosolic acetyl CoA up regulates synthesis of malic enzyme and citrate lyase |
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conversion of acetyl CoA to malonyl CoA |
rate limiting step of fatty acid synthesis |
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rate limiting step of fatty acid synthesis |
catalyzed by acetyl CoA carboxylase (ACC) converts acetyl CoA into malonyl CoA by carboxylation ACC adds a CO2 to acetyl CoA |
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Acetyl CoA carboxylase |
enzymatic and carrier protein functions biotin-dependent synthesized as an inactive protomer subunits serve as biotin carboxylase, a transcarboxylase, and a biotin carboxyl carrier protein |
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Allosteric regulation of ACC |
citrate and palmitoyl CoA |
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Phosphorylation/Dephosphorylation regulation of ACC (hormonal regulation) |
insulin |
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Induction/repression of ACC |
up-regulated by high carb/low fat diet down regulated by low carb/high fat diet |
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Fatty acid elongation |
occurs at fatty acid synthase complex 2 carbons of malonyl CoA sequentially added to growing fatty acyl chain to form Palmitate (16:0) After each addition, 2 reduction rxns occur that require NADPH and an intermediate dehydration |
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Fatty acid synthase |
large, multi-enzyme complex composed of 2 identical dimers, each has 7 catalytic activities and an acyl carrier protein (ACP) ACP segment has phosphopantetheine residue (PP) two dimers arranged in head to tail conformation |
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Further fatty acid elongation |
if you need chain longer than Palmitate (16C) must "prime" or activate chain elongation of chain occurs by addition of 2 Carbon fragments from Malonyl CoA occurs on ER membrane and catalyzed by Fatty acid elongase makes long chain fatty acids in brain |
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Desaturation of fatty acids |
occurs in ER intro of double bonds to form PUFAs fatty acyl-CoA desaturases (non-heme iron containing enzymes) most common location of double bond is between C9 and C10 |
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Essential fatty acids |
cannot be synthesized by human body need to get them from diet omega 3 fatty acids and omega 6 fatty acids |
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Examples of essential fatty acids |
Linoleic acid : (18:2, double bonds at 9,12) Linolenic acid (18:3, double bonds at 9,12,15) |
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Linoleic acid and linolenic acid |
precursors for eicosanoids: thromboxanes, prostaglandins, leukotrienes deficiency leads to: |
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Essential fatty acids required for: |
synthesis of arachidonic acid (C20, in brain) constituents of epidermal cell sphingolipds that function as skins water permeability barrier precursor of neuronal fatty acids |
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EPA |
eicosapentaneoic acid |
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DHA |
docosahexaenoic acid (fish oil) leads to optimal neuronal development in infants |
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Storage and Transport of Fatty Acids |
FA synthesized de novo or taken in diet-->converted to triacylglycerols (TAG) |
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TAG triacylglycerols |
major storage form of fuel |
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Synthesis of VLDL |
TAG packaged with apoproteins to form VLDL secreted in blood by liver via exocytosis |
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VLDL |
made of TAG, cholesterol, apoproteins |
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Regulatory factors released by adipose tissue |
Leptin and adiponectin (adipose tissue is hormonally active) |
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Leptin |
released when TAG levels are high binds to receptors, releases neuropeptides, tells body that you are full |
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Adiponectin |
abundantly secreted hormone by adipocytes binds receptors AdipoR1 and AdipoR2 stimulates AMPK and PPARalpha AMPK activation leads to uptake of fatty acids and glucose However, secretion is reduced as adipocytes get larger |
