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60 Cards in this Set
- Front
- Back
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Beta- Oxidation |
The release of energy from FA - four step enzyme catalyzed process that removes a 2C unit from a FA to make Acetyl-CoA - occurs at carboxyl end - leads to ATP production via Citric Acid Cycle |
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Triacylglycerols (TGs) as Storage: Pros |
The best storage fuel (> 2x energy of CHO) - highly reduced FA chain (lots of hydrogens) - very insoluble in water; store without raising osmolarity of cell - chemically inert
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Triacylglycerols (TGs) as Storage: Cons |
Hydrophobic nature means they must: - be emulsified - transport around the body is difficult (do not dissolve in blood) - need cofactors to react with an enzyme |
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Lipid Digestion and Transport: Step 1 |
bile salts emulsify dietary fats in the small intestine, forming mixes micelles |
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Lipid Digestion and Transport: Step 2 |
intestinal lipase's can then degrade tracylglycerols into monoglycerides, diglycerides, free FA and glycerol |
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Lipid Digestion and Transport: Step 3 |
products diffuse into epithelial cells where they are reconverted to TGs and packaged with dietary cholesterol |
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Lipid Digestion and Transport: Step 4 |
This repackaged cholesterol and apolipoproteins make chylomicrons |
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Lipid Digestion and Transport: Step 5 |
Chylomicrons move into the lymphatic system and then enter blood, carrying them to muscle and adipose tissue |
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Lipid Digestion and Transport: Step 6 |
In capillaries of these tissues the extracellular enzyme lipoprotein lipase. activated by apoC-II, converts TGs into fatty acids and glycerol; FAs enter the cells |
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Lipid Digestion and Transport: Step 7 |
In adipocytes/myocytes FAs are oxidized as fuels/re-esterified for storage |
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Perilipins |
family of proteins that restrict access to lipid droplets (so they don't mobilize unnecessarily) |
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Lipid Mobilization from Storage: Step 1 |
When blood glucose is low, epinephrine and glucagon are secreted |
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Lipid Mobilization from Storage: Step 2 |
(GPCR): cAMP is produced and PKA is activated |
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Lipid Mobilization from Storage: Step 3 |
Activated PKA has two actions: 1st- phosphorylates hormone sensitive lipase 2nd- phosphorylates the perilipins |
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Lipid Mobilization from Storage: Step 4 |
Transport perilipins are bound to CGI proteins; PKA separates them |
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Lipid Mobilization from Storage: Step 5 |
Free CGI proteins react with ATGL, a triglyceride lipase |
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Lipid Mobilization from Storage: Step 6 |
ATGL makes the TG a diacylglycerol and a free FA
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Lipid Mobilization from Storage: Step 7 |
Hormone sensitive lipase breaks the diacylglycerol into a monoglyceride and a FA
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Lipid Mobilization from Storage: Step 8 |
MGL separates the monoglyceride into a FA and glycerol |
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Lipid Mobilization from Storage: Step 9 |
FAs enter the bloodstream via albumin transporter |
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Fate of Glycerol |
Only contributes 5% of energy a) goes back to TG synthesis or b) used to synthesize G-3-P to use in glycolysis |
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Glycerol to G-3-P reaction: Step 1 |
Glycerol--> L-glycerol-3-phosphate - catalyzed by glycerol kinase |
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Glycerol to G-3-P reaction: Step 2 |
L-glycerol-3-phosphate--> Diydroxyacetone phosphate - catalyzed by glycerol-3-phosphate dehydrogenase |
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Glycerol to G-3-P reaction: Step 3 |
Dihydroxyacetone phosphate--> D- Glyceraldehyde-3-phosphate - catalyzed by triose phosphate isomerase - goes to Glycolysis |
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FA Activation to Enter the Mitcohondria |
Enzymes of FA oxidation are in the mitochondrial matrix - when over 14C, must undergo reaction to be activated so it can enter the carnitine shuttle |
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FA Activation: Process |
BOTH catalyzed by Fatty acyl-CoA Synthase - carboxylate on FA is adenylated by ATP to form fatty-acyl-adenylate -Co-A attacks the thiol group, displacing AMP and making Fatty-Acyl-CoA |
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Carnitine Shuttle: Step 1 |
Carnitine acyltransferase I removes CoA-SH from Fatty-Acyl-CoA and replaces it with Carnitine - outer mitochondrial membrane |
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Carnitine Shuttle: Step 2 |
Passage to inter membrane space via large pores Fatty-Acyl-Carnitine enters the matrix via facilitated diffusion through the Acyl-CArnitine/Carnitine Transporter |
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Carnitine Shuttle: Step 3 |
Carnitine on the FA is replaced by CoA-SH, catalyzed by Carnitine Acyl-Transferase II - carnitine re-enters inter membrane space using the same transporter |
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Beta-Oxidation of C16 FA: Step 1 |
Acyl-CoA-Dehydrogenase converts Fatty-Acyl to trans-delta^2-Enoyl-CoA - FAD reduced to FADH2 |
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Beta-Oxidation of C16 FA: Step 2 |
Enoyl-CoA Hydratase adds a water molecule to make L-Beta-Hydroxy-Acyl-CoA |
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Beta-Oxidation of C16 FA: Step 3 |
Beta-hydroxyacyl-CoA Dehydrogenase catalyzes conversion to Beta-ketoacyl-CoA - NAD reduced to NADH |
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Beta-Oxidation of C16 FA: Step 4 |
Thiolase (ACyl-CoA Acetyltransferase) catalyzes conversion to a C14 FA, Acyl-CoA and Acetyl-CoA |
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Beta-Oxidation: Full Process |
Seven passes through the path will fully oxidize a 16C yields: - 8 acetyl-COA (7th from final 2 C which do not undergo oxidation) - 7 FADH2 (1.5/ATP) - 7 NADH (2.5/ATP) - Total: 28 ATP and 7H2O
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Unsaturated FA Oxidation: C18: Step 1 |
Activated from Oleate to Oleate-CoA - goes through 3 cycle of Beta-oxidation to release 3-Acetyl-CoA |
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Unsaturated FA Oxidation: C18: Step 2 |
This leaves cis-delta^3-Dodecenoyl-CoA |
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Unsaturated FA Oxidation: C18: Step 3 |
Changed from cis to trans by delta^3-delta^2-Enoyl-CoA Isomerase - makes trans-delta^2-Dodecenoyl-CoA
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Unsaturated FA Oxidation: C18: Step 4 |
trans-delta^2-Dodecenoyl-CoA can go through 5 more cycles of beta-oxidation (releases total 9 acetyl-CoA) |
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Polyunsaturated FA Oxidation: C18: Step 1 |
Lineolate activated to Linoleoyl-CoA; goes through 3 cycles of beta-oxidation, releasing 3 Acetyl-CoA |
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Polyunsaturated FA Oxidation: C18: Step 2 |
The first double bond is oxidized to trans by delta^3-delta^2-enoyl-CoA Isomerase |
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Polyunsaturated FA Oxidation: C18: Step 3 |
After going through on beta-oxidation, hits second double bond: - cis/trans catalyzed by 2,4-dienoyl-CoA Reductase - NADPH dependent |
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Polyunsaturated FA Oxidation: C18: Step 4 |
double bond is moved over by enoyl-CoA Isomerase; can now go through Beta-Ox 4 more times (total 8 acetyl-CoA) |
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Odd #C FA Oxidation: C3: Step 1 |
Activated to Propionyl-CoA Propionyl-Co A Carboxylase carboxylates to form D-Methylmalonyl-CoA - requires Vit B7, ATP and Bicarbonate |
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Odd #C FA Oxidation: C3: Step 2 |
converted to L-Methylmalonyl-CoA via Methylmalonyl-CoA Epimerase |
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Odd #C FA Oxidation: C3: Step 3 |
Methyl-malonyl-CoA-Mutase catalyzes a intramolecular rearrangement making Succinyl-CoA |
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B-Ox in Other Organelles |
Differs in Two Respects a) first oxidative step passes directly to O2 (makes H2O2) in order to convert FADH2 back to FAD+ b) NADH cannot be re-oxidized; goes to mitochondria to do so |
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Beta-Ox Regulation |
- carnitine shuttles are the point of commitment for Beta-Oxidation - Malonyl-CoA the 1st intermediate of FA synthesis inhibits carnitine acetylteransferase 1, disallowing the FA into the cell - low ATP inhibits acetyl-coA carboxoylase (lipid synthesis) activating carnitine shuttle
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w-Oxidation in ER |
Oxidation occurs at the omega carbon (opposite way) - found in the ER of the kidney/liver - usually 10-12C FA |
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Omega-Oxidation: Step 1 |
- hydroxyl group to omega carbon via the enzyme mixed function oxidase |
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Omega-Oxidation: Step 2 |
Alcohol Dehydrogenase acts on the omega carbon - oxidizes the hydroxyl group to an aldehyde - NAD to NADH |
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Omega-Oxidation: Step 3 |
Aldehyde Dehydrogenase then oxidizes the aldehyde to a carboxylic acid - FA with carboxylic group at both ends; symmetry |
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Omega-Oxidation: Step 4 |
either end can be Beta-oxidized - final products (beside acetyl-coA's): Succinate and Adipate |
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Ketone Bodies |
Acetone, Acetoacetate and D-Beta-Hydroxybutyrate (same parent compound Acetoacytl-CoA) - formed in starvation/low carb - water soluble (blood) - produced in the liver when there is a build up of acetyl-CoA - acetone is exhaled - other 2 converted to acetyl-CoA in other tissues |
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Ketone Body Synthesis: Step 1 |
Thiolase catalyzes the condensation of two acetyl;-CoA molecules into Acetoacetyl-CoA (CoA-SH removed) |
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Ketone Body Synthesis: Step 2 |
Another Acetyl-CoA is brought in with water and made into HMG-CoA (catalyzed by HMG-CoA Synthase) - loss of another CoA-SH |
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Ketone Body Synthesis: Step 3 |
HMG-CoA Lyase removes an acetyl-CoA to make Acetoacetate |
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Fate of Acetoacetate |
a) catalyzed by Acetoacetate Decarboxylase (removes CO2--> Acetone) b) catalyzed by D-Beta-hydroxybutyrate Dehydrogenase (reducing of NADH--> D-Beta-Hydroxybutyrate) |
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Ketone Body Catabolism: Step 1 |
D-Beta-Hydroxybutyrate used as fuel; oxidized to acetoacetate by D-beta-hydroxybutyrate dehydrogenase |
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Ketone Body Catabolism: Step 2 |
Succinyl-CoA gives Acetoacetate a CoA; creates Acetoacetyl-CoA - catalyzed by Beta-ketoacyl-CoA Transferase |
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Ketone Body Catabolism: Step 3 |
Thiolase adds a CoA-SH and creates 2 Acetyl-CoA |
