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38 Cards in this Set
- Front
- Back
FA storage
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Triglycerides
de novo synthesis in liver from glucose |
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FA degradation (TG's)
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3FA's and one glycerol,
FA's go to liver ATP/NADH gluconeogenesis to muscle spares glucose for glucose dependent tissues |
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Describe degradation TG to FA in adipose and transport to appropriate tissues
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glucagon/epi activates HSL (hormone sensitive lipase, it's P'd)
TG-->3FA and glycerol(liver) FA goes out of adipocyte to blood and is bound to albumin goes to target tissue dissociates and binds to FABP |
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What tissue can FA not go to?
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brain
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FA transport into mitochondria once it hits target tissues
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has to be activated by tagging an acetyl on it, and has to be transported via citrate (except SCFA and MCFA)
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where do SCFA and MCFA's get activated?
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in the mitochondrial matrix
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what activates FA's?
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Fatty acyl-CoA synthetase, uses two high E bonds, driven by pyrophosphatase,
families of synthetases are based on chain length |
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Where does activation of LCFA and VLCFA's occur?
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mitochondrial intermembrane space (cytosol?)
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describe biochemically, the transport of activated FA into mito
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FA-SCOA --> FA-Carnitine
via CAT I |
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what is CAT I inhibited by?
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malonyl-Coa
lots of malonyl-CoA means synthesis is happening in the cytosol, so dont want to transport newly made FA into mito for degradation |
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CAT I
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rate limiting and regulated
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Deficiencies
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rare: CAT I II and translocase
CARNITINE DEFICIENCY decreased syn (in premies) defective membrane transporter in muscle heart kidneys treatment: aviodance of fasting, low LCFA intake, supplement with MCTG and carnitine |
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Beta oxidation of palmitic acid
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palmitic acid(16:0) + 7 FAD + 7 NAD --> 8 acetyl coa + 7 FADH2 + 7 NADH
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beta oxidation of stearic acid
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stearic(18:0) --> get 8 fadh2 8 nadh 9 acetylCoA
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steps of beta-oxidation
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FAD-deH (trans dbl bond between alpha and beta)
enoyl CoA Hydratase ( add water, get OH on beta C) beta-hydroxyacyl CoA DeH-NAD (double bond carboxy on beta C) Beta-ketoacyl CoA thiolase ( cleave at beta C, add CoASH) |
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which beta oxidation enzyme is chain-length specific
which transport enzyme is chain length specific |
acyl CoA DeH-FAD
fatty-acyl CoA synthetase (makes FA-SCoA) |
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for LCFA beta-oxidation what enzymes are in a membrane bound complex?`
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enoyl CoA hydratase
beta-hydroxyacyl CoA DeH-NAD Beta-ketoacyl CoA thiolase (the last 3) |
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what regulates beta oxidation (3)
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substrate concentration
malonyl Coa(inhibits CAT I) AcetylCoA/ free CoA ratio (thiolase uses free CoA in the last step, so decreased free CoA means decreased beta ox) |
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what does a high I/G ration do for FA synthesis? for beta-oxidation?
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high I/G increases synthesis and decreases oxidation
how?? |
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key regulated enzyme(s) of FA synthesis? or oxidation?
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synthesis: acetyl CoA carboxylase (makes malonyl coA, uses biotin PG)
oxidation: CAT I |
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how many ATP per C do you get for beta oxidation of FA? how many from glucose?
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8atp/C for FA
6 atp/C for glucose |
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Beta oxidation of odd-numbered FA's
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problem - 3C product eventually, left with propionyl CoA
add a C: CO2 ATP / Proprionyl CoA carboxylase biotin change from D to L: methylmalonyl CoA racemase change L-methylmalonyl CoA to succinyl CoA: methylmalonyl mutase Coenz B12 |
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what is the only glucogenic precursor from FA's?
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proprionate getting changed to succinyl CoA for the TCA cycle
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Beta-oxidation of unsaturated FA's
dbl bond at odd C |
problem: enoyl hydratase can't work on a cis kinked double bond
cleave normally till hit double bond use enoyl isomerase to transform cis dbl bond at 3 to trans dbl bond at 2 |
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beta ox of unsaturated
dbl bond at even C |
beta oxidize till hit dbl bond at C4, and start initial deH of cycle 5 by making dbl bond (trans) at alpha-beta C
use nadph and dienoyl CoA reductase to make trans dbl bond at beta-c3 shift trans dbl bond at 3 to C2 using enoyl isomerase this can then be used by enoyl CoA hydratase to finish cycle |
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what is required for VLCFA oxidation?
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peroxisome - specific fatty acyl CoA synthetase
ABC transporter (into perox) oxidase (direct reduction of O2) |
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draw out VLCFA degradation
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VLCFA --> FA-SCoa (synthetase)
FA-SCoa --> enoyl-SCoa (FAD-oxidase) Enoyl CoA -->BOH CoA(hydratase) BOH --> beta Keto (DeH/get NADH) Thiolase --> acetylCoA and eventually break down to MCFA MCFA is transported out to mito via peroxisomal CAT (uses carnitine, generates CoA) |
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Peroxisomal alpha oxidation of FA
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occurs at alpha b/c beta has a branch on it
shortens by 1C (CO2) phytanic acid (20C) to pristanic acid (19)which can do beta oxidation |
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how else can you ox branched FA?
minor pathway |
oxidation of methyl terminus (omega -ox)
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Synthesis of ketone bodies
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FA-> B-oxidation-> acetyl CoA
2AcetylCoA (2c) --> acetoacyl Coa(4c) + CoA (thiolase) acetoacyl Coa --> HMG coa (6c)+ CoA (HMG synthase) HMG Coa --> acetoacetate + acetyl CoA (HMG lyase) acetoacetate + NADH <-> BOH butyrate(BOH DeH) acetone can be produced but its a dead end |
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how many CoA's do you get? from KB synthesis
what do you use |
2 CoA
3 acetyl CoA's (regenerate 1) 1 NADH (interconversion from acetoacetate to BOH) |
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Regulation of KB synthesis
2 |
CoA supports B-oxidation
NADH from B-oxidation pushes acetoacetate to BOH |
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Utilization of KB (not by liver!)
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IN MITO
BOH -> acetoacetate+NADH (BOH deH) acetoacetate + Succinyl CoA --> acetoacyl CoA + Succinate (transferase) acetoacyl Coa + Coa <-> 2 Acetyl Coa (thiolase) |
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what is resting [KB]?
diabetic ketoacidosis[KB]? |
3-5 mM
up to 20 mM |
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X-ALD
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xlinked
adrenoleukodystrophy defect in ABC transporter for prox can't get VLCFA's into perox accumulate (esp in brain) childhood form: develops normally till school age, then dementia, adrenal insufficiency |
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Zellweger cerebrohepatorenal syndrome
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AR
VLCFA and phytanic acid accumulation low survival PEX Receptor found on the surface of peroxisomes recog's SKL on proteins |
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Refsum disease
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AR
phytanic acid storage disease (alpha-ox) defic in alpha-hydroxylase restrict dietary phytanic acid |
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MCAD
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medium chain acyl-CoA DeH
most common defect in B-oxidation usually less than 2, can die under 12C oxidation is greatly reduced, Hypoketosis and hypoglycemia (more glucose use cause no KB, and little gluconeogenesis b/c ATP and NADH to drive gluconeo come from beta-ox diagnosis: peal of carbons at c8 treatment: avoid fasting, carnitine supplementation, newborn screening |