Medical Biochemistry Exam 3 questions with answers, Exams of Medical Biochemistry

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Medical Biochemistry Exam 3 Lipoproteins Functions - ANSWERS: Keep their component lipids soluble as they transport them in the plasma Transport fat soluble vitamins such as A and E Lipoprotein Structure - ANSWERS: Contain triacylglycerols, cholesterol, phospholipids, and proteins (apolipoproteins) Lipoprotein Core - ANSWERS: Cholesteryl esters and TGs Lipoprotein Outer Layer - ANSWERS: Phospholipids, free cholesterol (nonesterified), apolipoproteins B (apoB) ApoB is embedded but ApoC and ApoE are only loosely bound so they can be exchanged between different particles Apolipoproteins - ANSWERS: Structural and Metabolic functions on lipoproteins Determine metabolic fate of lipoprotein particles through interactions with cellular receptors Regulate the activity of enzymes involved in lipid transport and distribution - ApoCII will activate LPL ApoCII activates - ANSWERS: Lipoprotein lipase Classes of Lipoproteins - ANSWERS: Chylomicrons Low Density Lipoproteins High Density Lipoproteins Very Low Density Lipoproteins Remnant particles (chylomicron remnants and VLDL remnants/IDL (intermediate density lipoproteins) - TG rich LDL - ANSWERS: Bad cholesterol Beta lipoprotein Mainly cholesterol Includes: B100 Low TAG HIGHEST cholesterol Negative charge HDL - ANSWERS: Good Cholesterol Alpha-lipoprotein Mainly protein Includes: AI, AII (C, E) LOWEST TAG High cholesterol Chylomicrons are neutral charge Cellular Uptake of Lipoproteins - ANSWERS: Mediated by apolipoprotein binding to receptors present on cell membranes Allows cells to acquire cholesterol and other lipids Key receptor is the LDL receptor Also have scavenger receptors LDL (apoB/E) Receptor - ANSWERS: Key lipoprotein receptor Expression is regulated by the intracellular cholesterol concentration Scavenger Receptor - ANSWERS: Collagen like triple helix structure Present on phagocytic cells like macrophages Not subject to feedback inhibition - they may overload the cell with the ligand they bind Do NOT bind normal LDL - they bind oxidized LDL - atherosclerosis Mutations in LDL receptors... - ANSWERS: Results in increased blood levels of LDL because cells cannot take up these particles at a normal rate Chylomicrons vs Capillary Walls - ANSWERS: Chylomicrons are too big to cross - instead they enter lymph vessels (lacteals in the gut) first Lipid Digestion/Absorption Efficiency - ANSWERS: Almost all FAs and 2-monoacylglycerols are absorbed Water insoluble lipids are poorly absorbed - only 30-40% of dietary cholesterol is absorbed Glycerol in the intestinal lumen is NOT used in the enterocyte for TAG synthesis - it passes directly to the portal vein Chylomicrons and the Lymph System - ANSWERS: Chylomicrons are too big to pass capillary walls so they go to lymph system from enterocyte They leave the system via the thoracic duct that empties into the left subclavian vein - so in the end the chylomicrons eventually make it to the blood circulation Abundant chylomicrons in plasma will give a milky appearance Chylomicrons eventually make it to blood via? - ANSWERS: Lymph system (lacteals) draining into left subclavian vein Lacteals - ANSWERS: Lymph system Chylomicron Maturation - ANSWERS: Nascent Chylomicrons are synthesized in intestinal epithelial cells, secreted into the lymph, ultimately pass into the blood and become mature chylomicrons Nascent Chylomicrons - ANSWERS: Synthesized in intestinal epithelial cells - already has Apo B-48 which is unique to chylomicrons Released by intestinal mucosal cell, functionally incomplete - will become mature in blood when it receives apoE and apoCII from HDL Apo B-48 - ANSWERS: Unique to chylomicrons Constitutes 48% of the protein encoded by this gene - Apo B-100 is synthesized by the liver and found in VLDL and LDL, represents the entire protein encoded B Apolipoprotein Gene - ANSWERS: Transcribed and translated in LIVER (hepatocytes) to produce Apo B- 100 In INTESTINAL cells there is a stop codon which produces a shorter version - Apo B-48 (chylomicrons) - after the RNAs have been processed, RNA editing converts a Cytosine to a Uracil producing the stop codon LPL - Chylomicron Activation - ANSWERS: The Apo CII on chylomicrons activate LPL What transports TGs synthesized in liver? - ANSWERS: VLDL VLDL acquires what in the blood? - ANSWERS: Cholesteryl esters and apolipoproteins CII and E from HDL Two routes of IDL after cleavage from VLDL by LPL - ANSWERS: Go to liver via Apo E receptor mediated endocytosis - ApoE is on the surface of IDL Be further processed by HTGL into LDL HTGL - ANSWERS: Hepatic Triacylglycerol Lipase IDL, LDL, Chylomicron lysosomal digestion products - ANSWERS: Cholesterol Amino acids Pi Fish Oil - ANSWERS: Can be used to combat LPL or ApoCII Deficiency Omega 3 fatty acids in fish oil lower plasma triglyceride concentration - can be substantial Can also be used as an anti-arrhythmic, particularly in patients who have already suffered a MI Gemfibrozil (Lopid) - ANSWERS: Antihyperlipidemic Activates LPL and lowers triglyceride levels in plasma Abetalipoproteinemia - ANSWERS: Caused by a lack of MTP Lack of MTP results in inability to assemble both chylomicrons in intestine and VLDL in liver - meaning few VLDL or chylomicrons are formed which allows TAG to accumulate in the liver and intestine - causing lipid malabsorption and steatorrhea - absorption of fat soluble vitamins (ADEK) is decreased due to less chylomicrons formed - LDL are low in blood MTP - ANSWERS: Microsomal Triglyceride Transfer Protein Accelerates the loading of apoproteins with triglycerides, cholesterol esters, and phospholipids - thus helping make lipoprotein particles Lack of MTP results in inability to assemble both chylomicrons in intestine and VLDL in liver - meaning few VLDL or chylomicrons are formed which allows TAG to accumulate in the liver and intestine - causing lipid malabsorption and steatorrhea - absorption of fat soluble vitamins (ADEK) is decreased due to less chylomicrons formed - LDL are low in blood MTP Inhibitors - ANSWERS: Are under investigation to lower blood lipid levels They can cause hepatic steatosis (fatty liver) so inhibitors specific to chylomicrons in intestine would be most beneficial Causes of Insulin Resistance in DM II - ANSWERS: Genetics Obesity Aging Sedentary Lifestyle DM II progression - ANSWERS: Insulin resistance -> hyper-insulinemia -> impaired glucose intolerance -> decline of B-cell function -> DM II Microvascular complications of DM II - ANSWERS: Retinopathy, neuropathy, nephropathy Macrovasculal Complications of DM II - ANSWERS: Cardiovascular disease, stroke DM I and Lipoprotein Levels - ANSWERS: Plasma chylomicron and VLDL levels are elevated in Type I DM resulting in elevated blood TAGs Low insulin in DM I leads to less LPL synthesis and secretion in the capillary beds of adipose tissue - leading to less chylomicron and VLDL degradation and thus a high TAG blood concentration Can also happed in DM II if the insulin secretion has become compromised due to chronic hyperglycemia and beta cell loss - beta cell burn out Steatorrhea - ANSWERS: fat in the feces; frothy, foul-smelling fecal matter Hepatic Steatosis in DM II - ANSWERS: Insulin resistance leads to increased lipolysis and production of free fatty acids free fatty acid availability increases ectopic deposition of TAG in the liver - leading to fatty liver - hepatic steatosis Steatosis results in non-alcoholic fatty liver disease which can end with a more serious condition, nonalcoholic steatohepatitis if accompanied by inflammation Free fatty acids also have a pro-inflammatory effect, which in the long term could impair insulin signaling NAFLD - ANSWERS: Nonalcoholic fatty liver disease NASH - ANSWERS: Nonalcoholic steatohepatitis HDL Metabolism - ANSWERS: Nascent HDL is synthesized in liver and intestinal cells and dumped into blood - most made in the liver Main apolipoproteins: ApoAI and ApoAII - also have apoCII and apoE HDL is a circulating reservoir of ApoCII and ApoE HDL picks up cholesterol from cell membranes Where does HDL get its cholesterol? - ANSWERS: Cell membranes HDL Cholesterol - ANSWERS: From cell membranes Ezetimibe - ANSWERS: Selectively inhibits cholesterol uptake in the small intestine - reduces chylomicron production and cholesterol deliver to liver Bile Acid Binding Agents - ANSWERS: Interrupt the enterohepatic circulation of bile acids in the intestine - causes more hepatic cholesterol t be diverted to new bile acid production - reduced availability of intrahepatic cholesterol increases LDL receptors and LDL clearance from circulation Niacin - ANSWERS: Inhibits VLDL production Increases LPL activity - promotes TG clearance from circulating VLDL particles Raises circulating HDL levels by impairing hepatic uptake of Apo A1 (HDL Apo Protein) Fibrates - ANSWERS: Enhances VLDL catabolism by increasing LPL synthesis via peroxisome proliferator- activated receptor alpha (PPAR-a) Raise HDL by stimulating the production of HDL associated apoproteins FFA? PPAR-alpha activators are called - ANSWERS: Fibrates Nuclear transcription factor Atherogenesis - ANSWERS: The process of forming atheromatous plaques in the inner lining of arteries Involves endothelial dysfunction, deposition of lipids in the arterial lamina, low grade inflammatory reaction, migration and proliferation of the vascular smooth muscle cells, and thrombosis An early atherosclerotic place can grow and ultimately occlude the vessel or it may not grow at all and heal Thrombus - ANSWERS: A blood clot Formation of blood clot - thrombosis Mural Intraluminal Thrombus - ANSWERS: Nonocclusive Layers of arterial wall - ANSWERS: Outer to Inner Adventitia External elastic lamina Tunica media (vascular smooth muscle) Internal elastic lamina Subintimal extracellular matrix (subintimal space) Endothelial Cell Lumen Oxidized LDL - ANSWERS: See diagram Too much NO can also be bad by oxidizing LDL Digestion and Absorption are regulated by... - ANSWERS: Hormones, nervous system, paracrine factors Disease: Maldigestion and Malabsorption respectively Key Clinical Signs of Malabsorption/Maldigestion - ANSWERS: Diarrhea, steatorrhea, weight loss Most common cause of carbohydrate malabsorption - ANSWERS: Lactase deficiency Absorption begins in... - ANSWERS: Jejunum However bulk of nutrients are absorbed in the ileum Each main type of nutrient undergoes digestion at multiple points... - ANSWERS: Meaning disruption at a single point is unlikely to cause a complete indigestion Functional Reserve in Digestion - ANSWERS: Pancreatic Disease manifests only after 90% of the pancreatic function is destroyed With surgical removal, the pancreas and small intestine can compensate digestion Pancreatic insufficiency has lingual lipase and gastric lipases compensating Enhancement of small intestine surface area - ANSWERS: Circular folds Villi Microvilli Microvilli - ANSWERS: brush border - contains enzymes (intrinsic enzyme) for digestion and transporters (transport locus) for absorption Has Glycocalyx, Tight Junctions Stomach - Poor Absorption - ANSWERS: 1. Lack of typical villus structures 2. Highly rich in tight junctions - only highly lipid soluble substances (ASA and ETOH) can be absorbed in small quantities Polysaccharides- plant and animal starches Disaccharides - sucrose and lactose Monosaccharides - glucose, fructose, galactose Starch - Amylase - ANSWERS: Starch consists of amylose (linear) and amylopectin (branched) - these polymers of glucose are partially digested by the enzyme amylase AMYLASE CAN ONLY CLEAVE ALPHA 1,4 NOT 1,6 - salivary and pancreatic Amylase digests starch and releases... - ANSWERS: 1. Maltose (1,4) and Isomaltose (1,6) 2. Maltotriose 3. Glucose oligomers 4. Alpha limit dextrin - still contains alpha 1,4 and alpha 1,6 bonds These products are further hydrolyzed on the surface of enterocyte to the monosaccharide glucose - brush border enzymes Brush Border Enzymes - ANSWERS: Hydrolases responsible for the sequential digestion of the products of luminal starch digestion - linear oligomers + alpha limit dextrins Glucoamylase Isomaltase Sucrase Maltase Trehalase Glucoamylase - ANSWERS: Digests both maltose and oligomers Isomaltase - ANSWERS: Digests isomaltose All carbs are broken down to monosaccharides by... - ANSWERS: Membrane bound enzymes present on the intestinal mucosal surface - enzymes on the GLYCOLAX SGLT1 transporter - ANSWERS: Sodium Glucose Linked Transporter Transports glucose and galactose Has both a Na and Glucose/Galactose binding site GLUT 5 - ANSWERS: fructose transporter Inducible Disaccharidases - ANSWERS: Disaccharidases are inducible EXCEPT for LACTASE Greater amount of a disaccharide = greater amount specific disaccharidase produced by the enterocytes Glucose/Galactose Malabsorption - ANSWERS: Causes severe diarrhea which is often fatal if glucose and galactose are not promptly removed from the diet Lactose Intolerance - ANSWERS: Reduced/No digestion of lactose Lactase enzyme is absent Most common in Asians African Americans are less tolerant to lactose compared to caucasians Tx: avoid dairy products or use a commercial lactase enzyme Yogurt is more tolerant than milk as it contains a bacterial lactase Lactose undigested by small intestine makes its way to large intestine where bacteria convert it into 2 (acetic acid) and 3 (lactic acid) carbon compounds with CO2 and H2 leading to diarrhea, bloating, and dehydration H2 can be measured in the breath Bacteria converts lactose into... - ANSWERS: Acetic Acid Lactic Acid H2 CO2 Seen in lactose intolerant individuals Preliminary Digestion Occurs in... - ANSWERS: Gut lumen with final stage occurring on intestinal mucosal surface SGLT1 is driven by... - ANSWERS: Na gradient created by basolateral sides of epithelial - lowers intracellular Na concentration to that less of lumen - higher to lower concentration Extra K ion leave the cells through leaky K channels Galactose + Glucose absorption is (blank) dependent - ANSWERS: Sodium dependent - due to SGLT1 Fructose is Na INDEPENDENT Pepsin Exopeptidases - ANSWERS: Once endopeptidases cleave proteins, exopeptidases find more free ends and chop amino acids one by one from peptide ends Remove aa one by one from N OR C terminus Aminopeptidases Carboxypeptidases Chymotrypsin - ANSWERS: Chymotrypsinogen is precursor Endopeptidase Cleaves at aromatic amino acids: Phe, Tyr, Trp, Leu? Elastase - ANSWERS: Proelastase is zymogen precursor Cleaves at hydrophobic amino acids: alanine, glycine, serine? Trypsin - ANSWERS: Trypsinogen is precursor Cleaves at basic amino acids Products of Peptidases - ANSWERS: 2-8 amino acids in length and free amino acids Carboxypeptidase - ANSWERS: A - cleaves at neutral amino acids B - cleaves at basic amino acids Chymotrypsin + Elastase - ANSWERS: Cleave large peptide into peptide with a C terminal neutral AA Carboxypeptidase A comes and cleaves further and creates small peptides and free neutral amino acids Trypsin + Carboxypeptidase B - ANSWERS: Trypsin cleaves large peptide into peptide with basic C terminal AA Carboxypeptidase B comes and cleaves peptide further into small peptide fragments and free basic amino acids The final digestion of di- and oligopeptides is carried out... - ANSWERS: In small intestine by membrane bound endopeptidases, dipeptidases, and aminopeptidases Some di and tripeptides are also digested inside epithelial cells Deficiency in pancreatic secretion - ANSWERS: 1. Chronic Pancreatitis 2. Cystic Fibrosis 3. Surgical removal of pancreas Digestion and absorption of fat and proteins are incomplete Results in steatorrhea and undigested protein in the feces Neutral Amino Acid Symporter - ANSWERS: Basolateral Short, polar, aromatic, and hydrophobic side chains Imino Acid Symporter - ANSWERS: Proline or OH-Pro Basic Amino Acid Symporter - ANSWERS: Basic amino acids Acidic Amino Acid Symporter - ANSWERS: Acidic amino acids Beta Amino Acid Symporter - ANSWERS: Beta alanine, Tau Defect in AA Symporter will affect - ANSWERS: Intestinal and RENAL absorption Hartnup Disease - ANSWERS: Congenital defect in the mechanism that transports neutral amino acids (TRYPTOPHAN) in the intestine and renal tubules Cystinuria - ANSWERS: A congenital defect in the transport of basic amino acids COAL Precipitation of cystine will form kidney stones (calculi) Most patients do no experience nutritional deficiencies of these amino acids because peptide transport compensates COAL - ANSWERS: Cystine, Ornithine, Arginine, Lysine Basic amino acids that absorbed in cystinuria Lipid Digestion starts in... - ANSWERS: The mouth - lingual And stomach - gastric lipase - acid stable Lingual and Gastric Lipase - ANSWERS: Lipid Digestion Lingual - mouth - more than 95% of the bile salts recirculate between the liver and ileum Bacteria in gut deconjugate and dehydroxylate bile salts Emulsification - ANSWERS: physical process of breaking up large fat globules into smaller globules Micelles - Lipid Digestion - ANSWERS: Micelles transport the lipids to the brush border of the enterocyte/mucosa Short and medium chain FA are taken up enterocytes without aid of micelles - helpful in medical nutrition therapy for individuals with malabsorption disorders CCK - Lipid Digestion - ANSWERS: Produced in small intestine in response to lipids and partially digested proteins entering the upper small intestine Acts on: - gallbladder - exocrine cells of pancreas - causing them to release digestive enzymes - decreases gastric motility - slower release of gastric contents Reduced absorption of fats leads to... - ANSWERS: Steatorrhea FA Absorption - ANSWERS: Diffusion - almost all absorbed Glycerol Absorption - ANSWERS: Diffusion Passes directly to portal vein to go to liver - Glycerol Kinase - not used in enterocytes for TAG synthesis 2-MAG Absorption - ANSWERS: Diffusion Cholesterol Absorption - ANSWERS: Diffusion NPC1L1 Lysolecithins Absorption - ANSWERS: Diffusion Leave enterocytes in Chylomicrons (exocytosis) SCFA and MCFA - Lipid Absorption - ANSWERS: Less than 10 carbons Pass through enterocytes to lacteals LCFA - Lipid Absorption - ANSWERS: Greater than 12 carbons Bound to fatty acid binding protein within the cell, and then transferred to ER for synthesis back into TAGs All major lipids resynthesized inside enterocytes are released out basolateral membrane via exocytosis Absorbed MAG and LCFA are re-esterified to form TG in the smooth ER Pancreatic Nucleases - ANSWERS: Split nucleic acids into nucleotides in the intestine Nucleotide Digestion - ANSWERS: Split into nucleosides and phosphoric acid by enzymes on luminal surface of the mucosal cells Nucleoside Digestion - ANSWERS: Split into constituent sugars (deoxyribose and ribose) and purine + pyrimidine bases Purines - ANSWERS: Adenine and Guanine Pyrimidines - ANSWERS: Cytosine and Thymine Purine and Pyrimidines are absorbed via... - ANSWERS: Active transport Nucleoside Transport - ANSWERS: Passive + active nucleoside transporters have recently been identified and are expressed on the apical membrane of enterocytes Two main groups of vitamins - ANSWERS: Fat Soluble Water Soluble Fat Soluble Vitamins - ANSWERS: ADEK Incorporated in micelles and absorbed via simple diffusion and packaged into chylomicrons - similar to long chain fatty acids Water Soluble Vitamins - ANSWERS: B and C With exception of B12 - are absorbed by Na+ cotransport Vitamin B12 absorption requires an intrinsic factor Vitamin B12 - ANSWERS: Requires intrinsic factor NOT Na Intrinsic Factor - ANSWERS: Secreted by parietal cells in the stomach Required for B12 transport Patients with Iron Deficiency - ANSWERS: Upregulation of ferrous reductase, DMT-1, and HT, thus more iron going to transferrin pathway of blood Iron Overload - ANSWERS: More iron converted to ferritin and less converted to transferrin Low Iron - ANSWERS: Anemia High Iron - ANSWERS: Causes hemosiderin to accumulate in tissues, producing hemosiderosis Hemosiderin - ANSWERS: An iron storage complex found within cells (not in blood) and appears to be a complex of ferritin, denatured ferritin, and other material Large amounts can damage tissues - hemochromatosis Hemochromatosis - ANSWERS: hereditary disorder with an excessive buildup of iron deposits in the body Pigmentation of skin, pancreatic damage with diabetes (BRONZE DIABETES), liver cirrhosis, hepatic carcinoma, gonadal atrophy Water Absorption - ANSWERS: Only 1% of fluid that is delivered to the GI tract is excreted Large intestine responsible for 20% of fluid absorption - osmosis Water absorption can be increased two fold with hypohydrated states - during aldosterone mediated increase in Na+ transport allowing more water to be osmotically absorbed Small intestine absorbs the most a day - 7L Diarrhea can be caused by... - ANSWERS: Can be caused by: 1. Nonabsorbable solutes present in the gut - osmotic diarrhea 2. Secretory agonists like microbial toxins - secretory diarrhea Osmotic Diarrhea - ANSWERS: Caused by malabsorption, digestive enzyme deficiencies or short bowel and inflammatory disease Secretory Diarrhea - ANSWERS: May be caused by infections Mainly caused by Crohn's disease, ulcerative colitis, IBS Monomeric Sugar Increase in Gut Lumen - ANSWERS: Increase in osmolality There is a compensatory decrease in the activity of brush border disaccharidases - this controls the osmotic load and prevents fluid shifts from circulation to gut lumen