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61 Cards in this Set
- Front
- Back
Apo B-100
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LDL, VLDL, IDL
555,000 Da VLDL secretion from liver Ligand for LDL receptor |
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Apo B-48
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Chylomicrons, Chylomicron remnants
260,000 Da Chylomicron secretion from intestine |
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Apo C-II
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VLDL, HDL, Chylomicrons
8,916 Da Activator of lipoprotein lipase |
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Apo E
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VLDL, IDL, HDL, Chylomicrons, chylomicron remnants
34,000 Da Present in excess in B-VLDL patients with type III hyperlipoproteinemia. The sole apoprotein found in HDL of diet induced hypercholesterolemic animals. Ligand for chylomicron remnant receptor in liver and LDL receptor |
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Apo B
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structural components of lipoproteins
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Apo C-II
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Interact w/ cell surface enzymes as cofactors or inhibitors during lipid transport
* activates LPL |
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Apo E or Apo B-100
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acts as ligands for lipoprotein receptors on the cell surface during lipid transport
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4 Mechanisms of Hormone Action
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1. Increase NZ substrate
2. Phosphorylate active site, changing its shape 3. Chance [allosteric affector] 4. Alter protein expression levels |
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Two main Cell Signaling Pathways by Fuel Metabolism Hormones
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1.) Polypeptide Hormones (Insulin, Glucagon) & Catecholamines (Epi/NE) bind to plasma membrane receptors to initiate action
2. Steroid Hormones (cortisol) pass directly through plasma membrane and exert effects on the cell nucleus |
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3 Basic Types of Signal Transduction Hormones that bind plasma membrane
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1. Receptor coupling to adenylate cyclase producing cAMP
2. Receptor Kinase activity 3. Receptor coupling to PIP2 |
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B-adrenergic receptor for Epi/NE
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- action through cAMP and PKA
- stim. glycogenesis & gluconeogenesis in mm. & liver - stim lipolysis in adipose |
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a-adrenergic receptor
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- action through phospholipase C
- use IP3 & DAG 2nd messengers - stim. vascular & sm contraction |
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Methylxanthines & Caffeine
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- inhibit cyclic nucleotide phosphodiesterase which recycles cAMP
- Prolongue the effects of Glucagon |
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2 problems with presented in TG digestion
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1. Lipids are poorly soluble
2. Hydrolysis of lipids releases products that tend to aggregate, blocking uptake by intestinal cells * Bile salts fix this problem, stimulated by CCK in duodenum |
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2 molecules that conjugate Bile salts
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- Taurine
- Glycine * lowers pKA, so they aren't charged at physiological pH * Makes bile more soluble |
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Critical Bile Salt level
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- concentration of bile salts at which micelles will form
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Dehydroxylation of Bile salts
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- at pos. 7
- makes bile salt less soluble and therefore more likely to be excreted in the feces - Called secondary bile salts when dehydroxylated |
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Secretin
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- Stim. release of bicarb to neutralize acidic stomach chyme in response to increased acidity in the SI
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Colipase
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- Acts in concert w/ pancreatic lipase
- anchors pancreatic lipase to lipid micelle - activates pancreatic lipase |
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Pancreatic Lipase
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- Breaks TG into --> 2FA & a monoacylglycerol
* the FA are cleaved from positions 1 & 3 on TAG - monacylglycerol and FA can be absorbed by intestinal epithelial cells |
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Olestra
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- Fat substitute
- Sucrose backbone - hard to digest by pancreatic lipase, therefore most passes into feces * Creates a problem b/c you don not absorb Vit ADEK which are fat soluble vitamins that are coabsorbed with dietary lipids |
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Orlistat (xenical or Alli)
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- Pancreatic Lipase Inhibitor used for weight loss
- forms a covalent ester bond with the active site of Serine 152 of human pancreatic lipase |
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Short & Medium Chain FA intestinal absorption
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- don't have to be in micelles, pass freely across the plasma membrane into intestinal epithelial cells
- Bind to serum albumin and transported across epithelial cells |
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Acyl CoA Synthetase
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- Converts FA to Fatty Acyl CoA
2 Places 1.) TG resynthesis in intestinal epithelial cells 2.) Activate FA for B-Oxidation *FACoA is a CoA thioester * 2 ATP equivalents are consumed in convervting FA-->FACoA |
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Differences in TG resynthesis in Liver/adipose and in Intestinal epithelial cells
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Intestinal Epithelial Cells
- 2MG reacts w/ individual FACoA first making diacylglycerol then finally TAG Liver/Adipose - Phosphatidic acid is the intermediate utilized for TG formations (2-MG takes it's place in intestinal cells) |
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Chylomicrons
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- Ball of TG, Phospholipids, Cholesterol, Cholesterol esters, fat-soluble vitamins, & Apo-Proteins
- Formed in intestinal cells after initial lipid digestion by and TG resynthesis in intestinal epithelial cells * if TG were no packaged into chylomicrons they would block blood flow |
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Four lipid classes in lipoproteins
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H-Philic/Polar --> exterior
- Phospholipids - Cholesterol H-Phobic/nonpolar --> Interior - TAG - Cholesterol Esters |
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TAG Transport
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Chylomicron & VLDL
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Cholesterol Transport
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LDL
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Cholesterol Reverse Transport
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HDL
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MTP (Microsomal Triglyceride Transfer Protein)
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- accelerates the transport of lipids across the ER membrane into the ER lumen during chylomicron synthesis.
- Also helps add Apo-B 48 during chylomicron assembly |
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Abetalipoproteinemia (Bassen-Kornzweig Syndrome)
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- Lack of MTP activity
- reduces formation of both chylomicrons & VLDL - leads to lipid malabsorption - Fat-Soluble Vitamin deficiency - Ataxia & nerve issues b/c reduced myelination |
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2 Proteins required for Nascent Chylomicron maturation
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- Apo CII
- ApoE * both come from interactions with HDL in blood - now considered mature chylomicrons |
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Lipoprotein Lipase (LPL) & what activates it?
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- In Blood
- Breaks down Chylomicrons into FA & Glycerol allowing absorption into Liver, muscle, & adipose - activated by Apo CII on mature chylomicrons |
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What Apo protein is recognized on chylomicron remnants by liver?
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Apo E
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2 reasons why TAGs are very efficient at storing fuel
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1.) stored in anhydrous form
2.) more chemically reduced than AA or monosaccharides |
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Metabolic Fates of FACoA
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1.) B-Ox (Energy)
2.) Plasma membrane (Cell Structure) 3.) TAGS (Storage) |
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CPT II Deficiency
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- Pt.s cannot process LCFA for energy
- symptoms: myoglobinuria, weakness, hypoglycemia - FA build up in blood & muscle causing damage |
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One Round of B-Ox
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1 NADH
1 FADH 1 Acetyl CoA 2C shorter Fatty Acyl CoA Steps: -Oxidation -Hydration -Oxidation -Thiolysis |
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Most Common FA B-Ox. Defect
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Medium Chain Acyl-CoA Dehydrogenase (MCAD)
- Acylcarnitines rise in blood & urine - Sleepiness, vomiting, hypoglycemic, hypoketotic, fatty liver, elevated blood levels of MCFA - treatment is to eat a low fat, high carb diet, and avoid long times between eating to avoid FA ox for E |
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Jamaican Vomiting Disease
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- Unripe fruit contains Hypoglycin, a toxin that inactivates short & medium chain acyl-coa dehydrogenases
- Severe hypoglycemia which may be fatal |
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Additional enzymes require for unsaturated FA Oxidation
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1.) Enoyl-CoA isomerase (used twice in Polyunsat.)
2.) 2,4 Dienoyl-CoA-Reductase (uses NADPH) * Monounsaturated only require enoyl-CoA isomerase, and only use it once |
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3 important control points of B-Ox.
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1.) Reg. of CPT-I in liver
2.) Release of FA from adipocytes 3.) Levels of ATP & NADH Fed state - Storage/FA synth Fasting state - FA ox. for E |
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Malonyl-CoA
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- Inhibit CPT-I in fed state
- A precursor for FA synth made from acetyl CoA by acetyl CoA carboxylase |
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Hormone Sensitive Lipase
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- releases FFA into blood during fasting state as a response to glucagon increase & insulin decrease
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alpha-oxidation
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- used for branched chain FA
- occurs in peroxisome - first cleaves at alpha carbon releasing a 1C unit - now beta oxidation proceeds alternating release of Acetyl-CoA(2C) & Propionyl CoA(3C) |
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omega-oxidation
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- FA oxidized at omega end (opp. end normally used in B-ox)
- FA are converted to dicarboxylic acids that can be released into urine (b/c they are now more soluble, neg. charge on each end) or beta-oxidized - normally a minor pathway, but more important when B-ox is defective. |
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Zellwegger's Syndrome
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- Defective Peroxisomal biogenesis
- can't process VLCFA & branched chain FA - fatal after 6 months of age - negatively affects liver & brain development - no treatment |
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Refsum's Disease
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- Deficiency in phytanoyl CoA Hydroxylase (a-oxidation)
- elevated phytanic acid in blood and tissues - neurological damage (blind & deaf) - treat w/ low phytanic acid diet ( no green vegetables) |
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Liver lacks this enzyme and therefore can't use KB for E
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- Succinyl-CoA transferase
- requires succinate |
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Galactose 1-P accumulation inhibits....?
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-Phosphoglucomutase
-preventing formation of UDP-Glucose, the precursor for UDP-Glucutonate, glycogen, glycoproteins, ect |
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a-lactalbumin
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- 1 of 2 subunits in lactase synthase (the other is galactosyltransferase)
- Synthesized after childbirth in response to prolactin - Lowers Km of galactosyltransferase for glucose to increase the rate of lactose synthesis - acts as a specifier protein by altering substrate specificity |
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2 subunits of Lactase Synthase
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- Galactosyltransferase
- a-lactalbumin |
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O-linked Glycoproteins are attached to .....(fxnal group) of ..... (AA)
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- OH
- Ser/Thr |
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N-linked Glycoproteins are attached to .... (fxnal group of .... (AA)
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- N
- Asn |
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2 Classes of N-linked Oligosaccharides
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1.) high Mannose
- only 2 GlcNAc & up to 9 Mannose - Complex |
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I-Cell Disease
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-Deficient Phosphoatransferase, which is required for tagging the terminal mannose w/ p-group
- therefore NZ secreted to EC space instead of lysosome - lysosomes become engorged and form inclusion bodies |
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Tay-Sachs
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-Lysosomal Storage Disease
-NZ Def: Hexosaminidase A - Mental Retardation, blindness, Cherry Red spot on macula, death between 3 &4 |
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UDP-Glucuronate is a precursor of...
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- Glucuronides
- Bilirubin Diglucuronide (conjugated) - Proteoglycans & glycoproteins |
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Reasons for increased bilirubin
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- Hemolysis (G6PD deficiency)
- Liver Disease - Premature Infants (low levels of conjugating enzyme) |
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Amino sugars used in the synthesis of GAGs are all derived from...?
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Glucosamine-6-Phosphate
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