Term
Unsaturated Fatty Acids, general facts |
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Definition
Polyunsaturated have double bonds that are always 3 carbons apart(separated by methylene group)
Fatty acids only lengthened or shortened from COOH end
Mammals cannot insert new double bonds beyond c9-10
Unsaturated FAs, Double bonds must be modified before B-oxidation. Normal DBs in Cis form, oxidation requires isomerization to trans form. |
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Term
Mans essential fatty acids |
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Definition
Linoleic(18:9,12) gives rise to Arachidonic acid
a-liniolenic(18:9,12,15) acid gives rise to W-3 FAs. |
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Term
Generation of Cytosolic Acetyl CoA (transport from mitochondria -> cytosol) |
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Definition
Acetyl-CoA + OAA -> Citrate(crosses membrane) + CoA-SH
In cytosol Citrate + CoA + ATP -> Acetyl CoA + OAA + ADP.
OAA + NADH -> Malate + Nad Malate + NADP -> Pyruvate + NADPH + Co2.
Pyruvate goes back into mitochondria. |
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Term
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Definition
Acetyl CoA + CO2 + ATP -> Malonyl CoA + ADP
Requires Biotin(Co2 carrier) covantly bound to lysine in schiff base. Malonyl-CoA inhibits B-oxidaiton.
Inactivated by High malonyl-CoA (Disintegration into monomers)
Phosphorylation -> Inactivates. |
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Term
Hormonal Control of acetyl CoA carboxylase |
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Definition
Insulin -> Dephosphorylationi of Acetyl-CoA carboxylase (activates)
Glucagon and Epi Inactivate. (cause FA and glucose mobilization)
Insulin -> protein phosphatase Glucagon/Epi -> cAMP-protein kinase
Long term: prolonged fat-free diet or CHO-rich diets -> Change in gene expression |
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Term
Reactions in fatty acid synthesis |
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Definition
1. Acetyl-CoA binds to phosphopantetheine site (ACP) 2. Acetyl group -> Cysteine 3. Malonyl-CoA forms thioester with ACP 4. Malonyl CoA condenses with Acetyl CoA and CO2 group is released. Creates B-ketoacyl
Than reduction, Hydration, Reduction
NADPH both reductions |
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Term
Fatty Acid synthase control |
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Definition
Enzymes that increase in well fed-state
Acetyl-CoA carboxylase, ATP citrate lyase, G-6-P deh, Fatty acid synthase
Fatty acid synthase overexpressed in some breast/ovarian cancers, also a potential target in obesity |
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Term
Fatty acids to triglycerides |
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Definition
FA are first activated, and than esterified to form triacylglycerol(TAG)
Glycolysis is livers main source of C for glycerol.
Liver has glycerokinase, Fat cell does not. |
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Term
Linoleic Acid -> Arachidonic Acid |
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Definition
Activate Linoleic with CoASH 1 desaturation, 1 elongation, 1 more desaturation.
Elongations always add 2 carbons. |
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Term
Polyunsaturated FA's can be oxidized non-enzymically |
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Definition
At high O2 FAs are susceptible to auto-oxidation or peroxidation.
From ease of drawing away hydrogen from methylene group(between two double bonds)
Single O atom is inserted creating reactive aldehyde group.
If malon-dialdehyde the 2 aldehyde groups appear. Can cross link protein(NH2 and SH groups) -> Lipofuscin accumulation. |
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Term
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Definition
c-AMP starts multiplicative cascade to start FA oxidation.
Lipid droplet unmasked by phoshporylation of perilipin
2nd TAG exposed to cleavage by intracellular Hormone-sensitive lipase. (activated by Epineph/glucagon)
PKA phosphorylates HS-lipase and per |
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Term
Hormonal Control of Lipolysis |
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Definition
GLucocorticoids, Growth and thyroid hormone, facilitate lipolysis via induction of lipolytic proteins GLucocorticoids induce HS-lipase. Insulin inhibits HS-lipase via dephoshporylation |
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Term
Adipocyte breakdown of lipids |
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Definition
Adipose tissue releases unesterfied fatty acids and glycerol.
Albuin is a non-covalent carrier.
Glycerol travels to liver because adipocytes lack glycerokinase(glycerol to DHAP) |
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Term
FA transport into mitochondria for oxidation |
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Definition
FA -> Fatty acyl-CoA. (formation of acyl thioester energy rich compound)
ATP -> AMP drives thioester formation Done by Fatty-acetyl-CoA Synthetases
Long chain Fa-CoA synthetase is outer membrane.
Medium and short chain in matrix. |
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Term
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Definition
Required for transport of long chain FAs into matrix
Carnitine is made from lysine and methionine(3-CH3s) -> Trimetyllysine -> carnitine.
FA transfered from acyl-CoA to -OH on carnitine by carnitine-acyl-transferase and ester bond is formed.
In matrix FA rebinds CoA-SH and carnitine comes off |
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Term
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Definition
Occurs in matrix of mitochondria. Oxidation by acyl-CoA deh -> FADH2 Hydration by Enoyl-CoA hydratase Oxidation by hydroxylcyl-CoA -> NADH deh Thiolysis by ketoacyl-CoA thiolase Yields Acetyl CoA |
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Term
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Definition
Level of HS-lipase and Lipoprotien Lipase. (main suppliers of FFAs)
2nd malonyl-CoA: Inhibits carnitine-acyl transferase
Carnitine-acyl transferase I in liver increased expression in prolonged fast. |
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Term
Indirect allosteric regulation of B-oxidation |
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Definition
Carnitine-palmitoyl transferaesI: Inhibited by malonyl CoA.
B-oxidation itself has no direct inhibitors, just transport into mitochondria of Acetyl-CoA is regulated. |
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Term
Degradation of Very long(>24 C) FA |
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Definition
In peroxisomes, uses H202
E-FADH2 + O2 -> E-FAD + H2O2
Same process as mitochondrial B-oxidation, but first reaction catalyzed by H2O2
Zellwegers sydrome: functional peroisomes are absent, cant degrade VLFA-> deficicent plasmalogen. |
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Term
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Definition
Abberent α-oxidation of branched FAs(peroxisome)
When B-carbon bears -Ch3, the α-carbon cannot be oxidized, phytanic acid accumulates.
Normally α-carbon hydroxylated in O2-Vit C- Fe++ requiring reaction.
Deficient in refums(Phytanate hydroxylase) |
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Term
Oxidation of Odd-chain FAs |
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Definition
Propionyl-CoA is glucogenic precursor(odd numbered are keto and glucogenic)
1st: Carboxylation. Proprionyl CoA -> D-methymalonyl CoA. Via propionyl CoA carboxylase, REquires biotin, CO2, ATP.
2nd racemerisation to L-methymalonyl CoA
3rd: Requires Cobalamin(Vit B12) L-methylmalonyl CoA -> Succinyl CoA by methymalonyl CoA mutase. |
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Term
Medium-chain acty-CoA dehydrogenase deficnecy |
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Definition
Catalyzes first reaction in B-oxidation of medium chain FA
Lipid deposition and fatty liver.
Incorrectly diagnosed as Sudden infant death syndrome sometimes.
Low-fat diet and avoid fasting, usually detected during fasting hypoglycemia |
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Term
Carnitine(vit B20) deficiency |
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Definition
Common cause is Acyl-CoA deh deficiency accumulated Fatty acids form carnitine esters and are excreted in urine. LInked to hypoketotic hypoglycemia. Muscle cramps, weakness. Lipid droplets in muscle. Fatty degeneration of liver. |
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