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Biochem Quiz 9
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88
Biology
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12/01/2011

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Term
What are the hepatic functions?
Definition
heme catabolism, carb/lipid/drug/bile acid metabolism, protein synthesis, protein catabolism,
Term
What are the markers of hepatic impairment in the plasma?
Definition
high bilirubin,prothrombin time, ammonia, cholesterol, triglycerides, drug t1/2, bile acids

low glucose, albumin, urea
Term
What proteins processing/synthesis is affected in liver disease?
Definition
albumin, coagulation factors II, VII, IX, X (post-translational carboxylation allowing them to bind Ca2+-prothrombin time), most plasma alpha/beta globins
Term
When are acute phase proteins synthesized and what stimulates their synthesis?
Definition
in response to inflammation/infection

stimulated by proinflammatory cytokines released by macrophages: IL-1, IL-6, TNF
Term
What are the functions of the acute phase proteins and where do you get the AAs to make them?
Definition
AAs from proteolysis of skeletal muscle

Function: opsonins (C-reactive protein)-phagocytize macromolecules released by damaged tissues or infective agents, complement factors-lysis/phagocytosize foreign molecues (nonspecific immune response), TNF/IL-1 stimulate breakdown of specific intracellular proteins by ubiquitin-proteosome mechanism, proteases inhibitors (a1-antitrypsin/antichymotrypsin)- inhibit proteolytic enzymes promoting the formation of fibroblast growth/production of CT (repair/resolution)
Term
What are serum proteins measurements used to monitor?
Definition
disease progress, response to treatment (CRP)
Term
What is associated with alpha1-antitrypsin and what happens when it is deficient?
Definition
has macrophage-derived elastase as primary traget, genetic defect results in liver disease as infant and lung disease as adult

in absense of a1-antitrypsin- elastase causes tissue destruction, severity of the liver disease depends on the nature of isoform that is deficient (allelic variation M, S, Z)
Term
What are diseases associated with ceruloplasmin deficiency or copper deficiency?
Definition
anemia (copper nutritional deficiency or ceruloplasmin deficiency)

genetic- Wilson's disease, damage to liver and CNS
Term
What is AFP and when is is elevated?
Definition
AFP- alpha-fetoprotein, functions similar to albumin in adult (replaced after 1st year of life)

elevated in pt w/ hepatocellular carcinoma and also ovarian/testicular/Presacral teratocarcinomas and germ cell cancer
Term
Where are xenobiotics metabolised and what happens when they are processed?
Definition
In liver-functions to regulate blood levels of these therapeutic agents, metabolizes some to FAs b/c they contain carboxylic acids (benzoate and salicylate)

Once processed- some lose therapeutic effect, others gain active form, some activated to carcinogenic forms (polycyclic aromatic hydrocarbons)
Term
What are the 2 phases of drug metabolism and what are the enzymes used?
Definition
Phase 1- results in oxidized compound by cytP450 enzymes in presenceof NADPH

Phase 2- consists of conjugation to a more soluble compound such as glutathione or glucuronic acid which allows it to excreted into either the bile or blood stream, enzymes- glucuronyl transferases and glutathione-S-transferases (induced by certain foods for protection against carcinogens)
Term
What is an example of drug hepatotoxicity?
Definition
drugs can be rendered poisonous through hepatic metabolism at certain levels
toxicity from tolerance level of individual- idiosyncratic drug toxicity: genetic or immunologic cause
Example-Acetaminophen at high doses, conjugatation with glucuronic acid/glutathione is overwelmed, excess is oxidized by cytP450 to NABQI/NAPQI which causes free radical mediated peroxidation of membrane fats/hepatocellular damage
Term
What treats acetominphen hepatotoxicity and how does it work?
Definition
NAC- works by restoring intracellular glutathione (via N-acetyl cystein) to promote detoxification, scavengers for free radicals to provide antioxidant effects, provides glutathione substitute, directly conjugates with NAPQI

greatest effect w/in 8 hrs of overdose
Term
What can alcohol consumption lead to?
Definition
alcoholic hepatitis, steatosis, cirrhosis
Term
What is the major pathway of alcohol metabolism?
Definition
Oxidative breakdown in liver into acetaldehyde and acetic acid (acetate)

acetaldehyde from ethanol via alcohol dehydrogenase then acetaldehyde dehydrogenase to synthesize acetate (both require NAD+ as cofactor)

2 forms of alcohol dehydrogenase-slow and fast
Term
What is the most sensitive enzyme indicatior of damage to liver from alcohol?
Definition
GGT: gamma-glutamyl transferase
Term
What does the muscle do with the acetate formed by the metabolism of ethanol in the liver?
Definition
acetate to acetyl CoA into the TCA cycle
Term
What is the enzyme deactivated in the Asian population and what are the symptoms? And what is a drug that is a long term inhibitor of this enzyme?
Definition
acetaldehyde dehydrogenase

inactivity leads to accumulation of acetaldehyde causing flushing, nausea, sweating, confusion

Antabuse (dilsulfiram)
Term
What is the minor pathway of alcohol metabolism and when is it used?
Definition
Only activated in high does of alcohol (enzymes have a higher Km than alcohol dehydrogenase)

Microsomal ethanol oxidizing system (MEOS)- contains P450 (2E1), found in liver smooth ER
Term
What accumulates as a result of alcohol abuse?
Definition
NADH and acetaldehyde
Term
What do high levels of NADH do?
Definition
inhibit formation of pyruvate- leads to lactic acidosis, hypoglycemia, and formation of ATP from NADH sparing fat in liver and causing accumulation of fat in the liver, decreased capacity to burn fat and therefore hepatic steatosis; also inhibits B oxidation of FAs and promotes synthesis of FAs increasing VLDL synthesis
Term
What are the acute effects of ethanol metabolism in the liver?
Definition
inference/inhibition of drug metabolism, acetate in the blood, ketoacidosis, hepatic steatosis, hyperlipidemia, hypoglycemia, lactic acidemia, gout
Term
What does acidic pH inhibit and what does this cause in combination with the high NADH? What disease can this cause?
Definition
inhibits pyruvate carboxylase that makes OAA from pyruvate and CO2

high NADH reverses malate dehydrogenase that makes malate from OAA and NADH, depletion of OAA for gluconeogenesis leads to hypoglycemia

hypoglycemia- fetal alchol syndrome (irreversilbe mental/physical damage)
Term
Why do you have a gouty attack after a night of drinking?
Definition
lactic acid competes with uric acid for excretion, catabolism of NADH to adenine and degradation of adenin produces uric acid
Term
Chronic alcohol intake induces synthesis of what detoxification system causing what?
Definition
induces synthesis of CytP450 MEOS and increased activity of CytP450 hydroxylase system increased detoxification of hydrocarbon dugs, increased activation of carcinogens, increased degration of steroid hrmones (gynecomastia/hypotrophy of testes-sterility, increased estradiol production)
Term
What drugs are sober alcoholics insensitive to? Why does the pt overdose on these when taken with alcohol?
Definition
insensitive to benzodiazapines and barbiturates (need higher dose for sedative effect) and when taken with alcohol there is a supersensitivity effect b/c MEOS inhibition by ethanol and toxic overdose death (common by benzodiazapines)
Term
What is Wernicke's syndrome?
Definition
Caused by thiamine deficiency secondary to alcohol antivitamin action, results in brain's inability to use glucose- results in encephalopathy, opthalmoplegia, ataxia, stupor, coma, death
Term
What is Korsakoff's syndrome characterized by?
Definition
inability to learn new material (anterograde amnesia), mild retrograde amnesia, impaired reasoning ability; if not severe may be corrected by thiamine therapy
Term
What are advantages of light alcohol intake?
Definition
1 drink for W, 2 drinks for M a day

reduced incidence of heart disease due to antioxidant effect of flavonoid/polyphenols

in red wine- antioxidant is catechin which inhibits oxidation of cholesterol

increases HDL in individuals with slow alcohol dehydrogenase
Term
What are the 3 biochemical tests of liver function?
Definition
Transmainases- AST/ALT are required for hepatic metabolism of nitrogen and carbs, both used as markers

ALP- has 2 isoenzymes in bone and biliary tract, moderate increase found in hepatitis/cirrohis, 2x increase in extraheptaic biliary obstruction
Term
What are the lipid soluble vitamins and what are the water soluble ones?
Definition
lipid- A, D, E, K
water-B1, B2, B3, B6, B12, C, folate, panthotenic acid, biotin
Term
True or False: Vitamins are needed in high amounts to exert their function so they are synthesized in the body as well as acquired in the diet
Definition
False- only need small amount and cannot be synthesized in the body
Term
What are the 4 main functions of vitamins?
Definition
coenzymes in metabolic pathways (water soluble vitamins), maining cell/tissue integrity (antioxidants), homrones, essential for physiological processes (vision, blood coagulation, etc)
Term
Where are vitamins absorbed?
Definition
Intestines, fat soluble vitamins packaged in chylomicrons into the lymphatics and then into circulation
Term
What water soluble vitamins are stored and where are fat soluble vitamins stored?
Definition
Water soluble-B12, B6
Fat soluble- in liver or adipose tissue
Term
Where can you get Vitamin A, where is it stored and what is its function?
Definition
Nutritional source- preformed vit A (animal liver), b-carotene (dark green leafy veggies)

stored in liver as retinylesters

function: vision- retinal part of rhodopsin in rod/cone cells, cell signaling- retinonic acid binds to intranuclear receptors to modulate gene expression (maintenance of epithelial integrity, spermatogenesis, embryonic development
Term
What are the symptoms of Vit A toxicity? What is affected in a Vit A deficiency?
Definition
dry skin, mouth sores, loss of appetite, vomitting, hepatomegaly, liver failure, teratogen

Deficiency- impaired vision (mild-night blindness, severe- complete blindness due to aberrant differentiaion of epithelial cells in eye), increased frequency of infections from mucosal epithelial layers having less integrity
Term
What are the functions of Vit D?
Definition
increases calcium absorption from intestine, decreases renal excretion of calcium, mobilizes calcium from bones
Term
What is affected in a Vit D deficiency? What are the symptoms of Vit D toxicity?
Definition
Deficiency- soft pliable bones, rickets in children, osteomalacia in adults

toxicity- loss of appetite, nausea, thirst, stupor, hypercalcemia (calcium deposits in kidneyes and arteries)
Term
What are the functions of Vit E?
Definition
main fat soluble antioxidant in body, protects membrane-lipids from free radical damage
Term
What happens in a Vit E deficiency?
Definition
hemolytic anemia in premature infacts (tocopherol aka Vit E stores not yet formed), nerve damage in older children/adults via myelin damage
Term
What is Vit K important for and what is it used to make?
Definition
blood coagulation, coenzyme for synthesis of gamma-carboxyglutamate residues in proteins which is essential for Ca2+ binding (coagulation factors VII, IX, V, and prothrombin and osteocalcin)

main sources: intestinal bacteria and green leafy vegetables
Term
What happens in a Vit K deficiency?
Definition
bleeding in newborns (no intestinal flora), bleeding may occur in adults if bacterial flora is killed by excessive antibiotics
Term
What is the drug antagonist of Vit K?
Definition
warfarin- an anticoagulant
Term
What is another name for Vit B1 and what are its 2 functions?
Definition
thiamine (active form: thiamine-pyrophosphate) functions: energy metabolism- coenzyme in oxidative decarboxylation (pyruvate dehydrogenase/a-ketoglutarate dehydrogenase in TCA, a-ketoacid dehydrogenase in degradation of branched chain AAs); pentose phosphate pathway-coenzyme for transketolase
Term
What happens in a Vit B1 deficiency?
Definition
pyruvate dehydrogenase/a-ketoglutarate dehydrogenase important in NS since glucose main source of energy for brain

deficiency cause Beriberi- infantile form: tachycardia, vomitting, convulsion; adult form: dry skin, irritability, disorderly thinking, progressive paralysis
deficiency in chronic alcoholism (Wernicke-Korsakoff syndrome)- alcohol impairs thiamine absorption from intestines, symptoms: apathy, loss of memory, confusion, inability to move eyes
Term
What is the function of Vit B2 (Riboflavin) and what are the symptoms of a deficiency?
Definition
Function- coenzyme in forms of flavin mononucleotide (FMN) and flavin adenine dinucleotdie (FAD)

Deficiency- cracked lips are corner of mouth (cheliosis), dermatitis, purple smooth tongue (glossitis)
Term
What is the function of Vit B3 (niacin) and what happens in a deficiency?
Definition
Function- precursor of NAD and NADPH, tryptophan can substitute for it

Deficiency- Pellagra- Dematitis, Diarrhea, Dementia, Death
Term
What happens in toxicity of Vit B3 and how is it used pharmacologically?
Definition
Toxicity- skin flushing, itching, tingling/burning sensation on skin

Pharmacology- drug to treat high cholesterol, reduces lipolysis in adipose tissue, reduces triglycerides, VLDL, LDL levels in blood
Term
What are the functions of Vit B6 (pyridoxine) and what are the symptoms of a deficiency?
Definition
Functions- active form, pyridoxal phosphate, is a coenzyme- transmination reactions, certain deaminations/decarboxylation (dopamine, histamine, sertonin synthesis), heme synthesis

Deficiency- hyperirritability, neuritis, convulsions
Term
What are the functions of Vit C (ascorbic acid) and what are the symptoms of a deficiency?
Definition
Function- collagen synthesis, neurotransmitter synthesis, tyrosine degration, antioxidant (scavenge free radicals, keep iron in Fe2+ state)

Deficiency- bleeding, brusing, delayed wound healing, loose teeth, extreme: scurvy
Term
What are the functions of panthotenic acid (no known deficiency)?
Definition
Function- precursor of CoA- energy production from carbs, FAs, AAs; sphingolipid synthesis (palmitoyl-CoA), cholesterol synthesis (acetyl-CoA), heme synthesis (succinyl-CoA), neurotransmitter synthesis
Term
What are the functions of biotin and where is it bioavailable (deficiency is rare)?
Definition
Function- coenzyme in carboxylation reactions (FA synthesis, gluconeogenesis, leucine degradation, propionyl CoA degradation)

Bioavailability- biotin in corn/soy, not so much in wheat
Term
What are the functions of iron and what is caused by its deficiency?
Definition
Toxic-has to be bound, part heme and non-heme proteins

heme- iron is chelated to porphyrin ring
non heme- iron sulphur clusters

Deficiency- causes anemima
Term
What are the differences between Menkes and Wilson's disease?
Definition
Menke's- deficient ATP7A, deficient intestinal uptake of Cu, symptoms-neurological effects, growth retardation, hypopigmentation, laxity of skin, treatment-copper histadine

Wilson's- deficient ATP7B, deficient excretion of Cu, symptoms- cirrhosis, liver failure, neurological defects, psychiatric symptoms, treatment- Cu restricted diet, Cu chelators, oral zinc tablets
Term
What are the functions of Zinc? What does a deficiency cause?
Definition
Function- wide variety of enzymes/proteins- oxidative phosphorylation, protection against oxidative stress, acid-base balance, protein degradation, transcription, wound healing, skin integrity, spermatogeneis, pancreatic function

Deficiency- Acrodermatitis enteropathica- deficient Zn transporter, red/inflammed patches of dry scaly skin that progress to blistered lesions, hair loss, diarrhea
Term
Why is iodine important? What does a deficiency cause?
Definition
Important- thyroid hormone synthesis

Deficiency- goiter: lack of iodine in diet (enlarged thyroid), cretinism in children: mental/growth retardation b/c limited iodine while in the womb
Term
What enzymes contain selenium? What disease does a deficiency cause?
Definition
Enzymes- glutathion peroxidase, thioredoxin reductase (antioxidants), thyroid hormone deiodinase (convert T4 into T3)

Deficiency- Keshan disease (China): cardiomyopathy
Term
What are the functions of folate?
Definition
participates in metabolic reactions (1 C transfer)- AA interconversion (specifically homocystein to Met where folate and B12 interact)
Term
What is coenzyme form of folate?
Definition
tetrahydrofolate (FH4)
Term
What are the 3 active forms of folate?
Definition
N5MetFH4, N10FormyFH4, N5,N10-methyleneFH4
Term
What is the main circulating form of folate and what does folate in food have with it?
Definition
Main circulation form- monoglutamate N5-FH4

in food- folate has 3 or more glutamates (polyglutamate) which are removed by conjugagses to enhance folate absorption in the GI
Term
What are the sources of 1 carbon units? What are the forms in the one carbon pool? What are the products after receiving one carbon?
Definition
Sources- serine, glycine, hisitidine, formaldehyde, formate

Pool- Formyl, methylene, methyl

Products- dTMP, serine, purines, B12-CH3
Term
Folate has a role in formation of what essential DNA molecules?
Definition
purines and pyrimidines
Term
What is methotrexate?
Definition
Analog of folate, since folate is so important in DNA synthesis methotrexate can compete (competitive inhibiotor) for dihydrofolate reductase in pyrimidine synthesis and act as a cancer therapy drug slowing the cancer progression
Term
What other diseases is methotrexate used to treat and what are the side effects?
Definition
RA, psoriasis, asthma, alcoholic cirrhosis, IBS

side effects- GI distress, severe folate deficiency/anemia

can't reduce methotrexate's efficiency by adding high doses of folate
Term
What are the best sources of folate?
Definition
liver, fortified cereals, legumes, leafy green veggies (less rich-eggs, oranges)
Term
How does alcohol affect absorption/storage of folate?
Definition
competes with its transport protein so interferes with absorption/storage
Term
What other drug inhibits folate absorption?
Definition
anticonvulsants
Term
What is the result of a folate deficiency and what can cause it?
Definition
deficiency- megaloblastic/macrocytic anemia

causes- low intake, inadequate absorption (alcoholism, anticonvulsants), increased requirement, compromised utilization (B12 deficiency), excessive excretion (long term diarrhea)
Term
What are the first cells to be affected by folate deficiency? What defect does it cause in the fetus?
Definition
RBC in bone marrow (high turnover rate), WBC synthesis also disrupted

may result in neural tube defects in fetus- spina bifida, anencephaly
Term
What happens in RBC in folate deficiency?
Definition
Not able to make DNA, RBCs grow large but can't divide/mature, continous hemoglobin synthesis etc lead to increased cell size, w/out folate cells remain in large immature form-megaloblasts (retain nuclei), w/ fewer mature RBCs the oxygen carrying capacity decreases causing megaloblastic anemia
Term
What are the symptoms of a folate deficiency?
Definition
inflammation of tongue/mouth (glossitis/stomatitis), abnormal pigmentation of skin, weakness, tiredness, diarrhea, poor growth, depression, mental confusion
Term
What synthesizes Vit B12?
Definition
bacteria, fungi, algae- complex strucutre containing cobalt
Term
How is Vit B12 absorbed and transported?
Definition
released from proteins by actio of HCl/gastric juices, free B12 binds to R-protein (transcobalamin I/haptocorrins) synthesized by salivary glands and then travels to small intestine where pancreatic proteases release it, IF binds to B12 and the complex travels to ileum where it binds to receptor for absorption

in enterocytes- B12 attaches to transcobalamin II to enter portal blood, delivery to tissues is done via receptor for complex, taken up by liver, bone marrow, and RBCs
Term
What are the functions of Vit B12?
Definition
required coenzyme in 2 conversions: methylmalonyl CoA to succinyl CoA by methylmalonyl CoA mutase (assay by Schelling test) and homocystein to met by methionine synthase/homocysteine methyl transferase (lack of met leads to abnormal myelin)
Term
What is the methyl donor group in met synthesis?
Definition
MTHF- methyltetrahydrofoalte

free THF to particpate in DNA synthesis
Term
What is the type of anemia that occurs due to Vit B12 deficiency and how is it caused?
Definition
Pernicious anemia- causes death w/in 2-5 years of diagnosis, juvenile form- defective production of IF by gastric parietal cells

symptoms- similar to folate deficiency (megaloblasts)

cause of pernicious anemia is true Vit B12 deficiency resulting from hampered absorption of vitamin due to lack of availability of IF
Term
What are some causes of true Vit B12 deficiency?
Definition
absence of IF, absence/defective synthesis of pancreatic proteases, bacterial overgrowth in small intestine, tapeworm infection, use of certain antiulcer meds (reduce acid synthesis), chronic malabsorption syndroms (AIDS), chronic pancreatic disease, absence/surgical removal of much or all of ileum/stomach (Crohn's disease)
Term
Which mechanism of B12 deficiency will become apparent fastest: vegan diet, ileal dysfunction or IF failure?
Definition
Ileal dysfunction fastest followed by IF failure and lastly vegan diet
Term
What are dietary sources of Vit B12?
Definition
organ meats, seafood, beef, eggs, hot dogs, ham, milk/milk products
Term
What are the treatments for defective Vit B12 absorption? What can mask the deficiency? What is the recommended course when it first presents?
Definition
Treatment- montly injection, use of Vit B12 nasal gel, weekly ingestion of B12 supplement with megadoses

can be masked by large doses of folate

preventatively FDA recommends intake of both then rectification after blood work
Term
What can be a result of B12 deficiency in the NS?
Definition
nerve degeneration producing sensory disturbances in legs, paresthesia, loss of concentration/memory, visual disturbances, disorientation, dementia, sore tongue, worst cases-loss of bowel/bladder control
Term
What is SAM? What is it used for? How is it related to B12?
Definition
SAM: S-adenosylmethionine- essential CH3 donor for synthesis of- Norepi to epi, guanidinoacetate to creatine (connect to lack of energy/tiredness), nucleotides to methylated nucleotides, acetylserotonin to melatonin

Met is methyl donor for SAM synthesis and Vit B12 is required for synthesis of Met from homocysteine (lack of B12, no Met, no SAM)
Term
What is the methyl trap hypothesis and what does it relate?
Definition
in absence of B12, THF is trapped in methyl-bound form N5-methyl-FH4 (MTHF), so shortage of coenzyme form of folate which inhibits DNA synthesis which thus causes Vit B12 deficiency seondary to folate deficiency and an accumulation of homocysteine (homocystinuria)
Term
What happens to the accumlated homocysteine in the methyl trap hypothesis?
Definition
methylated to form met (MTHF and B12 necessary) or condensed w/ serine to form cystathionine (pyridocxal phosphate/Vit B56 required)

cystathionine to cysteine to accumulation of cysteine which causes inhibitoin of cystationtine synthesis which leads to accumulatio of homocysteine which is released into the bloodstream and is linked to neurological and cardiovascular diseases by inhibiting glutathione perioxidase causing low glutathione, increased oxidized LDL and atheroscelerosis
Term
How can choline prevent homocystein accumulation?
Definition
degradation products of choline are involved in 1 C metabolism, choline can be oxidized to betaine and in liver it can donate a methyl group to homocysteine to form methionine

if SAM accumulates- glycine can be methylate to form sarcosine (N-methyl glycine)
Term
What is the cause of neural tube defects in folate deficient pregnancies?
Definition
N5-methyl-FH4 levels decrease due to mutation in N5,N10 methylene-FH4 reductase causing an elevation of homocysteine secondary to folate deficiency which makes enzyme thermolabile and inhibits DNA synthesis
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