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100 Cards in this Set
- Front
- Back
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Where does FA synthesis occur?
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In the cytoplasm
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What is the source/ingredient for FA synthesis?
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AcCoA from the mitochondria
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How does AcCoA from mitochondria get to the cytoplasm for FA synthesis?
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Via the Citrate shuttle on the inner mito membrane!
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What are the steps in FA synthesis?
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AcCoA + CO2 from biotin
Malonyl-CoA FA synthesis by FAS complex |
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Where does FA DEGRADATION occur?
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In the mitochondria - where it's products will be consumed!
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What has to happen to FA's first in the cytosol before they can get to the mitochondria?
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Complex with CoA via FA CoA Synthetase to make ACYL-COA
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What shuttle then takes Acyl-CoA from the cytosol to mitochondria?
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Carnitine shuttle
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What inhibits the Carnitine shuttle?
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Malonyl CoA
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What happens if there is a Carnitine deficiency?
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The mitochondria cannot utilize long-chain FA's and they accumulate and are toxic!
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What is the process of Acyl-CoA degradation in the mitochondria? What is the final product?
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B-oxidation - product is AcCoA
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Where are KETONE BODIES made?
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In the liver
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What are the 2 ketone bodies?
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-B-hydroxybutyrate
-Acetoacetate |
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Where do ketone bodies get USED?
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-Muscle
-Brain |
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When are Ketone bodies ELEVATED?
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-Diabetic ketoacidosis
-Prolonged starvation |
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What are Ketone bodies made from?
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HMG-CoA
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What does the Brain do with ketone bodies?
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Metabolizes them to 2 AcCoA
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What is a classic sign of overproduction of ketone bodies?
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Fruity breath
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What will a urine test for ketones be able to detect?
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ONly ACETOACETATE - not B-hydroxybutyrate!!!
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So what would a urine test in diabetic ketoacidosis most likely show elevated?
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Acetoacetate
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What is the RLS in Cholesterol synthesis?
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HMG-CoA Reductase - takes HMG-CoA to Mevalonate
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What happens to 2/3 of plasma cholesterol after synthesis?
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Esterification by LCAT
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What drugs inhibit HMG-CoA Reductase?
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Statins!
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What are the essential fatty acids?
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Linolenic acid
Linoleic acid |
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What is dependent on these essential fatty acids?
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Eicosanoid synthesis - Prostaglandins and Leukotrienes!
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What can take the place of Linoleic acid if it is absent?
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Arachidonic acid
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What is the first thing that happens to Triglycerides when you eat them?
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Pancreatic lipase breaks them down in the small intestine!
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What happens to the FFA products of pancreatic lipase?
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Enterocytes take them up, and convert back FFA-> TG for packaging into chylomicrons.
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What do Chylomicrons consist of?
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Triglycerides + Lipoproteins A, B48, C2, and E
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What is A1?
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LCAT activator
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What is B48?
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Mediator of Chylomicron secretion
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What is C2?
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Cofactor for LPL
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What is LPL?
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Lipoprotein Lipase
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What is E?
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It just mediates extra remnant uptake
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So where do Chylomicrons go after being made in enterocytes? What happens to them?
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Into circulation - get degraded by Lipoprotein Lipase to produce Chylomicron REMNANTS
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What does a Chylomicron remnant go?
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To the liver
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What does the liver do with chylomicron remnants?
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Makes VLDL
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What is the main thing that distinguishes lipoproteins made by the liver from chylomicrons?
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Liver puts B100 into them
Chylomicrons lack B100 |
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What is B100?
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The component of lipoproteins that binds LDL receptor!
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What happens to VLDL when produced from liver?
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Gets chewed up by LPL again to produce IDL and LDL; both go back to the liver again.
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What enzyme degrades the TG's that remain in IDL?
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Hepatic TG lipase
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What enzyme degrades TG stored in ADIPOCYTES?
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Hormone sensitive Lipase
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Why is modified LDL bad?
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It forms ATHEROSCLEROTIC PLAQUES
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So what are the 3 main components that make up LIPOPROTEINS?
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-Cholesterol
-Triglycerides -Phospholipids |
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What lipoproteins carry the most CHOLESTEROL?
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LDL AND HDL
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What does LDL do with cholesterol?
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Carries it from LIVER to TISSUE
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What does HDL do with cholesterol?
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Carries it from PERIPHERAL TISSUE to LIVER
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Which cholesterol is good/bad?
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LDL = bad
HDL = good |
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What are the apolipoproteins in Chylomicron?
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A, C, E, B48
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Where is Chylomicron produced?
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Intestinal epithelial cells
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What is the function of Chylomicron?
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Carries DIETARY TrY to periph tissues, and Dietary CHOLESTEROL to the liver.
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What are 3 things caused by excess Chylomicrons?
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-Pancreatitis
-Lipemia retinalis -Eruptive xanthomas |
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What is the main function of VLDL? What apolipoproteins does it have?
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Delivers hepatic triglycerides to peripheral tissues; has B100, C2, E
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Where is VLDL made, and what does excess cause?
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-Liver
-Excess = pancreatitis |
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How is IDL formed?
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By degradation of VLDL
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What does IDL express in apolipoproteins?
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B100 and E only (no C2)
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What does IDL do?
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Takes Try/Cholesterol back to liver to make LDL
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What is the function of LDL?
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Delivery of hepatic cholesterol to peripheral tissues
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What apolipoprotein does LDL have?
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ONLY B100
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How is LDL formed?
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By LPL modification of VLDL in peripheral tissue!
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How does LDL get into target tissues?
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By RECEPTOR-MEDIATED ENDOCYTOSIS when it binds LDL-receptor on target tissues.
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What are 3 clinical manifestations of EXCESS LDL?
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-Atherosclerosis
-Arcus corneae -Xanthomas |
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What is the function of HDL?
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Carries peripheral cholesterol BACK to the liver.
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Which familial dyslipidemia has high levels of LDL? Why?
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Type IIa - it has defective LDL receptors
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Where does heme synthesis take place?
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In both the mitochondria and Cytosol!
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What is the first step in Heme synthesis, and what are the ingredients/enzyme? Where?
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Succinyl CoA + Glycine make d-Aminolevulinic Acid by d-ALASynthetase; on the inner mitochondrial membrane.
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Why is the first step important?
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This is the RLS, the committed step in Heme synthesis.
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What enzyme catalyzes the next step in heme synth and what can inhibit it?
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ALA dehydrogenase - Can be inhibited by LEAD poisoning
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What is the product of ALAD?
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Porphobilinogen - gets put into the cytosol
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What happens to Porphobilinogen next?
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4X Porphobilinogens get condensed into Pre-Uroporphyrinogen
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What enzyme catalyzes condensation of 4 PBG's?
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Uroporphyrinogen I Synthase - UROS
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What is the result of LACK of Uroporphyrinogen I Synthase?
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Acute Intermittent Porphyria
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What accumulates when there is lack of Uroporphyrinogen I Synthase/UROS?
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-dALA
-Porphobilinogen |
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What are 5 symptoms of Porphyria?
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-Painful abdomen
-Pink urine -Polyneuropathy -Psycholog disturbance -Precipitated by drugs |
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What enzyme is deficient in Porphyria cutanea tarda?
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UROD - Uroporphyrinogen Decarboxylase
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What accumulates in UROD deficiency?
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Uroporphyrin
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What color is Uroporphyrin?
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Tea colored
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What is the last step in heme synthesis?
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Protoporphyrin -> Heme
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What enzyme catalyzes Heme formation from Protoporphyrin and what does it use?
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Ferrochelatase - uses IRON Fe2
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What steps does Lead poisoning inhibit?
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Both Ferrochelatase and ALAD
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What accumulates in Heme poisoning?
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ALA and Protoporphyrin
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What is HEmoglobin composed of?
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4 pp subunits - 2a, 2B
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What are the 2 forms in which Hemoglobin exists? Which has high vs low affinity for O2?
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Taut - LOW affinity for O2
Relaxed - HIGH affinity for O2 |
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Why do things that shift the Hb-O2 dissociation curve to the RIGHT, cause its affinity to decrease?
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They favor the TAUT form of Hb over the Relaxed form!
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Why does Fetal hemoglobin have HIGHER affinity for O2 than adult?
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Because HbF has LOWER affinity for 2,3-BPG, which causes dissociation otherwise.
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Where does O2 bind heme?
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To the Fe2+
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Where does CO2 bind heme?
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At the N-terminus - NOT Fe!
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What form of Hb does CO2 favor for binding?
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TAUT
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And what does CO2 binding to Hb do to O2 binding?
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Promotes O2 unloading
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What is this effect of CO2 binding to Hb and promoting O2 unloading called?
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NEGATIVE allosteric regulation
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What is COOPERATION?
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When O2 binds it favors the binding of the next O2!
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What does the combination of Cooperative binding of O2, and Negative allosteric regulation of CO2 result in?
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The sigmoidal shape of the Hb-O2 dissociation curve!
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What are 2 molecules that modify Hb so much that it leads to decreased O2 sat AND blood O2 content?
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-Methemoglobin
-Carboxyhemoglobin |
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What is Methemoglobin?
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Hemoglobin that has OXIDIZED Fe - Fe3+
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Why is Oxidized Fe in Methemoglobin bad?
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It has HIGH affinity for CN-, but does NOT BIND O2 as readily
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What is the state of Fe in normal hemoglobin?
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Reduced; Fe2+
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What is the treatment for toxic levels of Methemoglobin?
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METHyline blue
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What is given in cases of CN- poisoning? Why?
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NITRITES - they oxidize hemoglobin to methemoglobin
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Why on earth would you want to OXIDIZE Hb to Methb, to treat CN poisoning?
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Because actually CN preferentially binds MetHb, thus gets EXCRETED faster.
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What is CARBOXYHEMOGLOBIN?
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Hemoglobin bound to CO instead of O2
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Why would CO bind to Hb instead of O2?
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IT has 200X higher affinity than O2!
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