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Use of Ketone bodies
- Produced in liver
- Used by heart muscle/kidney
- Starvation: brain
- Excess Ac-CoA - low OAA in TCA
- Diabetics: acetone breath
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Liver can do what with Acetyl-CoA
When low insulin/high beta oxydation, A-CoA exceeds Oxaloacetate, this means there are leftover A-CoA
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Ketone bodies
- Acetoacetate
- beta-hydroxybutyrate
- -circulating fuels produced by liver, non-glucose foods during fasting Acetone
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Physiological Conditions that Promote Ketogenesis
- Fasting/starvation
- Diabetes Ketogenic diet
- -High fat
- -Newborn
- All occur during low insulin
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Ketogenesis
- Occurs in liver
- Occurs when fat breakdown is predominate
- Not enough oxaloacetate to ferry all a-CoA into TCA
- Excess TCA becomes acetoacetate, 3-hydoxybutyrate, and acetone
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Transition from Acetyl-CoA to Acetoacetate, Acetone and beta-Hydroxybutyrate
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Acetoacetate/beta-hydroxybutyrate export
Exported as source of energy for heart, skeletal muscle, kidney and brain
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Glucose export from liver
Exported as fuel for brain/other tissues.
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Regulation of FA metabolism
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Cholesterogenesis
- Formed from A-CoA
- Major synthesis sites: liver, intestine, adrenal cortex and the gonads.
- Takes place in cytoplasm (unlike cytoplasm)
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Source of all carbons in cholesterol:
Acetate
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Origin of Cytoplasmic Acetyl-CoA Precursor
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Stage One of Cholesterol Synthesis
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Second Stage of Cholesterol Synthesis
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Stage 3 of Cholesterol Synthesis
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Stage 4 of Cholesterol Synthesis
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Stage One Step One: Acetyl-CoA to Acetoacetyl-CoA
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Stage One Step Two: Acetoacetyl-CoA to HMG-CoA
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Stage 1 Step 3: HMG-CoA to Mevalonate
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Stage 2 Step One: Mevalonate to Activated Isoprenes
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Stage 2 Step 2: Mevalonate to 5-Pyrophosphomevalonate
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Stage 2 Step 3: 5-Pyrophosphomevalonate to 3-Phospho-5-pyrophosphomevalonate
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Stage 2 Step 4: 3-phospho-5-pyrophosphomevalonate to
delta3-Isopentenyl pyrophosphate/Dimethylallyl pyrophosphate
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Stage 3 Step 1: Isoprenes (5-C) to Farnesyl (15-C)
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Stage 3 Step 2: Two Farnesyl-PP (15-C) Condense Head-to-head to Squalene (30-C)
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Stage 4 Step 1: Squalene Cyclization Forms Steroid Nucleus
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Stage 4 Step 2: Squalene Cyclization Forms Steroid Nucleus
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Stage 4 Step 3: Lanosterol to Cholesterol
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Synthesis of Cholesterol Esters
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Regulation of HMG-CoA Reductase Synthesis by Cholesterol
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Regulation of Cholesterol Synthesis
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Cholesterol as Steroid Precursor
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Lipid Linked Membrane Proteins
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