Term
| Functions of cholesterol (4). |
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Definition
1)Stabilize membranes,
2)Make bile salts to digest fat,
3)Synth vit E/A/Ubiquinone,
4)Precursor of steroid hormones. |
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Term
| What are the sources of C atoms for cholesterol synth. |
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Definition
| AcCoA from glucose, FAs, AAs, even alcohol. |
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Term
| How does insulin effect HMGCoA reductase? |
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Definition
| deP/activates as well as increases txn via SREBP. |
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Term
| How do LDLs promote CV disease? |
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Definition
| Immune response --> macrophage uptake --> foam cells --> swelling/inflammation |
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Term
| Where in cell and in which tissues is cholesterol synth? |
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Definition
| Cytosol/ER of all tissues, esp liver. |
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Term
| Rate limiting step of cholesterol synth and how is it regulated? |
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Definition
HMGCoA Reductase (HMGCoA+2NADPH-->Mevalonate+NADP);
inhib by AMP, cholesterol, glu;
stim by insulin, ATP. |
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Term
| How are serum cholesterol levels regulated? |
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Definition
| Uptake of LDL into cells by LDL receptors, receptor mediated endocytosis. |
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Term
| Treatments to lower cholesterol? |
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Definition
HMGCoA reductase inhibiting statins,
Positively charged bile salt resins. |
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Term
| How do bile salt resins lower cholesterol? |
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Definition
| Bind bile salts which are then excreted causing body to synth more from cholesterol. |
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Term
| How do cells protect against ROS? |
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Definition
| Protective enzymes (incl superoxide dismutases, catalase, glutathione peroxidase) & non-enzymatic mechanisms (GSH, NADPH, vit E, vit C) |
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Term
| Why is a free radical reactive? |
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Definition
| Unpaired e- in outer orbital wants to pair up w another e- to achieve stability. |
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Term
| How are ROS produced in RBCs? |
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Definition
| Nonenzymatic oxdn of hemoglobin, certain drugs/foods. |
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Term
| What types of damage do ROSs cause to cells? |
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Definition
Proteins-inactivate enzymes, promote, aggradation, degradation.
Lipids-lipid peroxidation, oxidation of polyunsaturated lipids which destroys mbrnes (destroys pmf!).
DNA/RNA-cleaves phosphodiester bond, base-mispairing. |
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Term
| What is lipid peroxidation? |
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Definition
| Peroxidation of many lipids to form lipid radicals + lipid aldehydes |
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Term
| Why is glutathione the most abundant chemical in cells? |
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Definition
| Most important antioxidant! 1)Reqd co-factor for glutathione transferase enzyme, 2) can react directly w some ROS to detoxify. |
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Term
| Which ROS is the most powerful oxidant? |
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Definition
| Hydroxide (OH. @ physio pH) |
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Term
| At which step are most super oxide radicals from the respiratory chain produced? |
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Definition
| Ubiquinone/CoQ step = Q + e- --> QH. + e- --> QH2 |
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Term
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Definition
| Removes toxins in liver via it's heme w bound iron - produces some ROS. |
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Term
| Why is brain prone to oxidative damage? |
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Definition
1) Monoamine oxidases remove nts but produce lrg amts of H2O2,
2) Brain is high in iron --> Fenton rxn --> hydroxyl radicals. |
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Term
| ROS enzymatic protectants? |
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Definition
| SODs, Catalase, Glutathione (req selenium) |
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Term
| ROS biochemical protectants? |
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Definition
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Term
| How do VitC/E/GSH work together to fxn as antioxidant? |
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Definition
Vit E donates H and becomes radical itself --> either:
a) 2 E radicals excreted or
b) VitC will restore.
Then either a) 2 VitC radicals excreted or
b) Glutathione restores and -->GSSG. |
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Term
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Definition
| When exceeds ferritin's binding capacity (most iron stored w ferritin, an iron storage protein) |
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Term
| What are 2 beneficial axns of oxygen radicals? |
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Definition
1)activated under conditions of low oxidant stress to prevent high levels of oxidant stress,
2) NADPH oxidases in macrophages&neutrophils --> respiratory burst. |
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Term
| What is result of NADPH oxidase deficiency? |
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Definition
| Chronic Granulamatosis. Missing-->die w/i 1mo. Deficiency-->incr suscebtibility to disease/tumors. |
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Term
| How does asbestos cause damage? |
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Definition
| Contains iron --> elastase in lung tissue v sensitive to ROS. |
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Term
| What is hemochromatosis and how is it treated? |
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Definition
| Iron overload; by adding iron chelator (desferrioxamine) which prevents iron from entering Fenton pathway. |
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Term
| Which neurogenerative diseases are caused by oxidant damage? |
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Definition
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Term
| How does ischemia reperfusion cause injury? |
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Definition
During prolonged ischemia ATP is broken down producing xanthine. Normally xanthine dehydrogenase oxidases xanthine to NADH but under stress and because of the new availability of O2 (from reperfusion) it is converted to xanthine oxygenase which still forms NADH but using O2 (rather than NAD+) as cofactor --> results in superoxide radicals.
In addn QH2 has accumulated due to resp chain back-up. |
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Term
| How can ischemia reperfusion injury be prevented? |
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Definition
| Addition of antioxidants (ie C, E, chelators, glutathione) to reperfusion soln. |
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Term
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Definition
1)Synth new protein,
2)Synth regulatory enzymes in response to metabolic conditions,
3)Synth nitrogeneous metabolites,
4)Provide energy via their degradation,
5)Provide Cs for gluconeogenesis and FA synth. |
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Term
| What does a pos or neg nitrogen balance signify? |
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Definition
| Pos=N intake>excretion (growth, pregnancy; Neg=intake |
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Term
| Which proteins have slow turnover rates? Fast? |
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Definition
| Slow = structural proteins, tissues; Fast = hormones, digestive enzymes, nts, rate limiting enzymes, oxidized proteins from ROS rxns. |
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Term
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Definition
| Tags protein for degradation. |
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Term
| What is major cofactor for AA metabolism and what is its function? |
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Definition
| B6=Pyridoxal Phosphate, transfers amino grp from AA-->aKG to form Glutamate + aKetoAcid. |
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Term
| How are AAs used as an energy source? |
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Definition
Degraded to pyruvate, AcCoA, TCA cycle intermediates --> 1)oxidized,
2)converted to glucose & stored as glycogen, or
3)converted to FAs& stored as adipose triacylglycerols. |
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Term
| Importance of transamination in AA metabolism? |
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Definition
| Removes amino grp from AAs to collect into a common pool as glutamate which can then enter the urea cycle for detoxification. |
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Term
| Clinical significance of GOT/GPT? |
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Definition
| Presence in blood signifies tissue damage, esp liver. |
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Term
| Which are the essential AAs? |
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Definition
| PVT TIM HALL (Phe, Val, Trp, Thr, Iso, Meth, His, Arg, Lys, Leuc) |
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Term
| Rxn catalyzed by Alanine Amino Transferase? Opposite rxn? |
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Definition
| Alanine+aKG-->Pyruvate+Glutamate; opp via Glutamate Pyruvate Transaminase (GPT). |
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Term
| Rxn catalyzed by Aspartate Amino Transferase? Opposite rxn? |
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Definition
| Aspartate + aKG --> OAA + Glutamate; opp via Glutamate Oxaloacetate Transaminase (GOT). |
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Term
| What are the 3 nitrogenous excretory products of the body? |
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Definition
| Uric acid, creatinine, ammonia. |
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Term
| How is excess amino nitrogen excreted? |
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Definition
| Collected as glutamate --> glutamate releases amino grps as ammonia --> enters urea cycle in liver --> excreted. |
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Term
| What are the 2 diff carbamyl phosphate synthetase rxns and where in cell do they occur? |
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Definition
| CPSI-->1st/RLS of urea cycle (CO2+NH4+2ATP-->Carbamoyl Phosphate+2ADP),mito; CPSII-->pyrimidine synth, in cyto. |
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Term
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Definition
| 1)NH3 is basic-->incr blood pH, 2)Combines w aKG-->Glutamate which reqs pulling aKG outa Krebs, 3)Combines w Glutamate-->Glutamine which is an excitatory nt. |
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Term
| Symptoms of ammonia intoxication? |
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Definition
| GI irritability, N/V, lethargy, neurological disturbances, coma, death. |
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Term
| Is arginine essential and why? |
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Definition
| Not in adults bc Arginosuccinate-->Arginine+Fumarate (urea cycle). |
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Term
| What is cyclical about the urea cycle? |
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Definition
Last step is arginine-->urea+ornithine,
ornithine re-enters cycle via ornithine+carbamoylP-->citrulline+Pi. |
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Term
| What mito exchange transporter is reqd for urea cycle? |
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Definition
Citrulline for Ornithine.
Ornithine needs to get into mito to combine w Carbamoyl P from CPSI rxn, Ornithine+CarbamoylP-->Citrulline, Citrulline mito-->cyto to enter urea cycle. |
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Term
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Definition
| Blood Urea Nitrogen, diagnostic for kidney fxn since kidney filters & removes urea. |
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Term
| What is most common inborn error of metabolism of urea cycle? |
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Definition
| OTC (Ornithine TransCarbamylase) def. |
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Term
| How can ammonia toxicity be prevented if someone has a urea cycle enzyme def (4)? |
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Definition
1)Low protein diet,
2)maintain blood pH w acetate, which is acidic,
3)clean gut of bactera,
4)benzoate/phenylacetate remove glycine/glutamine, taking NH3 with it. |
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Term
| How does muscle ammonia get to liver to enter urea cycle? |
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Definition
In muscle: NH3+Glutamate-->Glutamine (via Glutamine synthase)-->blood-->
In liver: Glutaminase hydrolyzes --> Glutamate+NH3,
NH3-->urea cycle,
Glutamate+NADP-->aKG+NADPH+NH3 via glutamate dehydrogenase. |
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Term
| Is glutamate an essential AA? Why or why not? |
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Definition
| No, can be produced via reversible glutamate dehydrogenase rxn in liver: Glutamate+NADP<-->aKG+NADPH+NH3 |
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Term
| What will be found in high levels in the blood after a high protein meal? |
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Definition
| Glutamine & Glutamate, carrying a-Amino grps muscle-->liver. |
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Term
| Where do first 2 steps of urea cycle occur? Last 3? |
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Definition
| 1st 2 in mito, last 3 in cyto. |
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Term
| Energetic cost to push 1 NH3 thru urea cycle? |
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Definition
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Term
| What can assaying ammonia level in blood tell us? |
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Definition
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Term
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Definition
| Activated by NAGA, whos synth from glutamate + AcCoA is activated by arginine. |
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Term
| How are the urea cycle and citric acid cycle linked? |
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Definition
Fumarate-->malate (hydration) --> OAA (oxidaton); OAA-->1)+AcACoA-->citrate-->Krebs,
2)gluconeogenesis,
3)pyruvate,
4)aspartate via transamination-->urea cycle. |
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