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53 Cards in this Set
- Front
- Back
fenestrations in sinus endothelium cells of liver
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mean diameter 100 nm-free diffusion of small molecules, but not particles the size of chylomicrons (chylomicron remnants are smaller and can pass directly to hepatocytes)
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1/4 of liver lysosomes are located
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in Kupffer cells
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stellate cells (aka perisinusoidal or Ito cells) fxns
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lipis filled cells and serve as primary storage site for vit A; control hepatic CT turnover and ECM, regulate contractility of sinusoids
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pit cells
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NK cells; liver-associated lymphocytes
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xenobiotics
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cmpds with no nutritional value and are potentially toxic
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phase 1 rxn
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take lipophilic cmpd and oxidize, hydroxylate, or hydrolyze via enzymes
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conjugation aka phase II rxns
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add negatively charged group like glycine or sulfate to molecule
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what is used to clear steroid hormones from circulation
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sulfation
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what can sulfate be obtained from
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degradation of cysteine or methionine
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P450-dependent mono-oxygenase system
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oxidative, peroxidative, reductive degradation of exogenous or endogenous substances
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key enzymatic components of P450 system
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flavoprotein NADPH-cytochrome P450 oxidoreductase and cytochrome P450
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cytochrome P450 fxn
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terminal e- acceptor and substrate-binding site of microsomal mixed-function oxidase complex
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nomenclature of P450 enzymes
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CYP2E1 = CYP is cytochrome P450 family, 2 is subfamily, and E denotes ethanol, and 1 denotes specific isoenzyme
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CYP3A4
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accounts for 60% CYP450 enzymes in liver and 70% cytochrome enzymes in gut wall enterocytes
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HMGCoA reductase inhibitors require what for degradation
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CYP3A4
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cytochrome P450 isoenzyme commonalities
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found in smooth ER, bound to lipid portion of membrane (phosphatidylcholine), inducible by presense of own best substrate, generate reactive free radical cmpd as intermediate
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vinyl chloride
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used in synthesis of plastics and can cause angiosarcoma of liver of exposed workers
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what is vinyl chloride activated by
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phase I rxn to reactive epoxide via CYP2E1-product can react with DNA or other cellular molecules
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Aflatoxin B1
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made more toxic by P450 (CYP2A1); produced by fungus Aspergillus flavus on peanuts
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acetaminophen metabolism in liver
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glucuronylated or sulfated for safe excretion by kidney; toxic intermediate N-acetyl-p-benzoquinoneimine (NAPQI)
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NAPQI normal formation with acetaminophen therapeutic levels
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<10% forms NAPQI which can be handled by glutathione detoxifying system (phase II rxn)
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what enzyme produces NAPQI
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CYP2E1 (induced by alcohol)
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how do ammonia groups travel to liver
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on glutamine and alanine-liver converts teses ammonia nitrogens to urea for excretion in urine
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what is the only organ that can produce ketone bodies
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liver, but it can't use them for energy
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when are ketone bodies produced
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rate of glucose synthesis is limited and fatty acid oxidation occuring rapidly
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what does albumin carry
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fatty acids, steroids, hydrophobic aas, vitamins, drugs
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portal hypertension causing ruptured esophageal varacies causes
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bleeding-metabolized by GI bacteria which release ammonium ion and enters portal vein-liver can't handle all the ions and they pass into circulation contributing to hepatic encephalopathy; also, clotting is decreased due to low liver fxn causing prolonged bleeding of varacies
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O-linked sugars secreted by liver
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most sugars secreted by liver are O-linked; carb attached to protein at its anomeric carbon through a glycosidic link to -OH of a serine or threonine residue
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N-linked sugars
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N-glycosyl link to amide nitrogen of asparagine residue
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N-acetylneuraminic acid (NANA)
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aka sialic acid; an O-linked sugar; 9-carbon sugar synthesized from fructose 6-phosphate and phosphoenolpyruvate
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major fxn of pentose phosphate pathway
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generation of NADPH and 5-carbon sugars-used to keep glutathione reductase going and generation of ribose
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what does the liver use NADPH for
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biosynthesis of fatty acids and cholesterol; also for other biosynthetic rxns like proline synthesis and P450 rxns
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energy supply for liver
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ATP, UTP, GTP, reduced NADPH, acyl CoA thioesters
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major fuels used by liver after mixed meal containing carbs
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glucose, galactose, and fructose
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why is glycolysis rate increased after glucose meal
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PFK-2 active, thus PFK-1 is activated by fructose 2, 6-bisphophate
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what determines rate liver uses glucose
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activity level of glucokinase
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fructose 6-phosphate and glucokinase
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high levels of fructose 6-phosphate promote interaction of glucokinase with RP
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high levels of glucose and fructose 1-phosphate with glucokinase
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block glucokinase from binding RP and promote dissociation
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when do fructose 2,6-bisphosphate levels increase
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in presence of insulin-increases glycolysis rate
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increased glucagon levels cause
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protein kinase A activation so that PFK-2 is phosphorylated and inactive = glycolysis slows down and gluconeogenesis enhanced
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major fuel in liver during fasting
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long-chain fatty acids (palmitic, stearic, and oleic)
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length of long-chain, medium chain, and short chain fatty acids
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12-20; 4-12; and 2-4
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where are sites for oxidation of medium chain fatty acids
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liver and kidney
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Zellweger (cerebrohepatorenal) syndrome
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rare inherited absence of peroxisomes in all tissues; accumulate C26-38 poluenoic acids in brain tissue due to defective peroxismal oxidation for myelin synthesis
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Peroxisome proliferator-activated receptors (PPARs)
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role in liver metabolism-in liver, direct activity of genes involved in fatty acid uptake and B and w-oxidation of fatty acids
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lack of PPARa in mice causes
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inability to increase rate of fatty acid oxidation leading to excessive fatty acid build up in hepatocytes, inability to make sufficient glucose and ketone bodies
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major urinary metabolite of aspirin in humans
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salicylurate
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why is there a relatively high level of triacylglycerols in ppl w/acute and chronic hepatitis, cirrhosis, or other diffuse hepatocellular disorders
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activities of both LPL (lipoprotein lipase) and HTGL (hepatic triglyceride lipase) are reduced
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Low LCAT levels with high triavylglycerol levels cause what composition changes in LDL particles
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high triacylglycerol and cholesterol ester poor
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branch-chain aas that can be used as fuel by most cell types
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valine, leucine, and isoleucine
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how do skeletal muscles, kidney, and intestinal mucosa send nitrogen to liver
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alanine
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how do skeletal muscles, lungs, and neural tissues send nitrogen to liver
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glutamine
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what other way does the kidney send nitrogen to liver
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serine
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