Term
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Definition
| 2 Acetyl-CoA -> Acetoacetyl CoA + CoA Via thiolase Acetoacetyl CoA + Acetyl CoA -> HMG CoA + CoA Via HMG-CoA synthase(mitochondrial) Acetoacetate + NADH -> (β) hydroxybutyrate + NAD Acetoacetate also spontaneously decarboxylates. to Acetone + CO2 |
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Term
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Definition
HMG- CoA synthase is rate limiting step.
Acetoacetyl CoA + Acetyl CoA -> HMG CoA
Stimulated by fasting, fat-feeding and insulin deficiency. |
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Term
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Definition
β-hydroxybutyrate + NAD → NADH + H+ + Acetoacetate
Acetoacetate + Succinyl-CoA → Acetoacetyl-CoA + succinate
Via Succinyl CoA transferase(not in liver)
Acetoacetyl-CoA + CoASH → 2 Acetyl-CoAs via Ketothiolase |
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Term
Metabolic States of liver.
Well Fed vs Starvation |
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Definition
Well fed: no ketogenesis.
Low glucagon:insulin. Malonyl-CoA up.
Starvation: High glucagon:insulin Malonyl-CoA down.
Glucagon stimulates ketogenesis by limiting formation of malonyl-CoA(phoshporylates/inactivates) |
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Term
| Enzymes Induced during fasting/starvation |
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Definition
Carnitine Palmitoyl-Transferase I
(break down of Fatty acids)
HMG-CoA synthase
(ketones)
Four gluconeogenic enzymes
Various transaminases |
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Term
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Definition
Triggered by insulin insufficiency and glucagon excess.
In patients with Type 1 DM(low blood sugar for extended periods of time)
Glucagon -> Lipolysis -> FFAs -> hepatic output of ketone bodies -> ketoacidosis |
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Term
| Arachidonic Acid synthesis |
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Definition
Can be made 2 ways.
Linoleic -> Arachidonic via desaturation -> elongationi -> desaturation. CoASH required.
Or
Release of arachidonic from phosphatidyl Inositol. Released by phospholipase(PLPA2)
Arachnidonic Acid is precursor to leukotrienes, Thromboxanes and prostablandings |
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Term
| Cyclo-oxygenases(COX) / Prostaglandin Synthase |
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Definition
Membrane bound with 1 heme group
Cyclooxygenase portion produces Prostaglandin G2
Peroxidase portion produces prostaglandin H2. Glutathione oxidized.
PGG2 and PGH2 prostaglandins are very reactive and unstable. Precursors to other prostaglandins and thromboxanes |
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Term
| Regulation Of Cyclooxygenase(COX) |
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Definition
Aspirin and Ibuprofen block Cyclooxygenase activity of COX1/2
(block serine residue by adding acetyl group)
COX-1: Constitutive enzyme
CoX-2: Indubicble in response to inflammation. Supressed by glucocorticoids.
Cox2 specific inhibitors: Viox, Bextra, Celebrex (Coxib) |
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Term
| EIcosanoids: PGI2 and TXA2 |
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Definition
Common precursors is PGH2
Prostaclycin: PGI2 produced by intact vascular endothelial cells, inhibits platelet aggregation, causes vasodilations
Thromboxane(TXA2): produced by platelet, stimulates platelet aggregation, Vasoconstriction. |
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Term
| Synthesis Of leukotrienes |
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Definition
2 lipooxygenase reactions make hydroperoxy derivative(HPETE) from arachidonic acid -> Leukotriens
Glutathione(LTC4) is modified LT, removal of amino acids produces LTD4 and LTE4. |
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Term
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Definition
Powerful constrictors of bronchial and intestinal smooth muscle.
Leukotrienes are stable.
LTC, LTD, LTE implicated in bronchoconstriction in asthmatic patient.
LTC4, LTD4 are components of slow reacting substance of anaphylaxis. Much more portent than histamine. |
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Term
| Steroidal anti-inflammatory drugs(SAIDS) |
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Definition
Glucocorticoids(Cortisol and cortisone)
Block phoshpolipase A2 and relase of Arachidonic Acid
Blocks production of all eicosanoids |
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Term
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Definition
Aspirin, indomethacin, ibuprofen
Inhibit COX enzymes
Still can produce 5-HPTE(Leukotrienes)
Aspirin therefore contraindicated in asthma. (Arachidonic acid must go into leukotrienes as COX is blocked) |
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Term
| Prostaglanding vs Thromboxan structure |
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Definition
Prostaglandin: 5 membered carbon containing ring
Thombroxanes: 6 membered oxygen contraining ring |
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