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Biochem 28, 29 and 30
drew
73
Medical
Graduate
03/16/2009

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Term
Lesch-Nyhan Syndrome
Definition
loss of HGPRTase activity. leads to gout, severe mental retardation, and a tendency for self-mutilation (biting of the hands and lips). Allopurinol reverses the buildup of urate found in these patients, but does not alter the neurological defects
Term
Two drugs used to treat Gout
Definition
Colchicine: blocks microtubule synthesis but works here by blocking inflamation.
Allopurinol: a suicide inhibitor of xanthine oxidase
Term
(PRPP)
Definition
5-phosphoribosyl-1-pyrophosphate: reacts with hypoxanthine and xanthine in the purine salvage pathway and is involved in the committed step of de nova synthesis of purines through formation of 5-phosphoribosylamine
Term
HGPRTase
Definition
hypoxanthine-guanine phosphoribosyl transferase: enzyme that salvages hypoxanthine and xanthine by reaction with PRPP
Term
Cause and mechanism of SCID
Definition
Cause: lack of adenosine deaminase or a lack of purine nucleoside phosphorylase causes T-cell dysfunction
Mechanism: build up of dATP
potentially inhibiting production of all dNDPs by ribonucleoside diphosphate reductase blocking DNA replication.
Term
How does alcohol lead to gouty attacks
Definition
It causes increased breakdown of hepatic ATP
Term
common intermediate in pyrimidine sythesis
Definition
orotate
Term
Vitamin B12 (cobalamine)
Definition
cofactor of methionine synthase, converts homocysteine to methionine. The only other human enzyme requiring B12 converts methylmalonyl CoA to succinyl CoA and is involved in odd-chain length fatty acid degradation and branch-chain amino acid degradation
Term
B12 deficiency results in elevated what in the blood?
Definition
methylmalonyl CoA
Term
methionine synthase
Definition
enzyme involved in
regenerating tetrahydrofolate, while synthesizing methionine. Requires B12 as a cofactor
Term
intrinsic factor
Definition
required for B12 absorption in the ileum.
Term
pernicious anemia
Definition
B12 defiency due to lack of intrinsic factor
Term
Symptoms of B12 defiency
Definition
neurologic dysfunction (numbness,
spastic gait, confusion and dementia) likely resulting from SAM S-adenosylmethionine defiency and megaloblastic anemia (can be masked by excess folate)
Term
Acyclovir
Definition
analog of guanosine in which the ribose ring is disrupted. Normal cells will not scavenge this analog, but the thymidylate kinase produced by herpesviruses will act on it.
Term
Which base can be synthesized as the free base?
Definition
pyrimidines
Term
RNR
Definition
ribonucleoside diphosphate reductase. Converts NDPs to deoxyNDPs
Term
5-Fluorouridine (administered as Adrucil, Efudex, or Fluracil)
Definition
converted by salvage pathway to 5-fluorodeoxyuridylate (F-dUMP. Suicide inhibitor of thymidylate synthase, blocks dTMP production
Term
Methotrexate
Definition
competitive inhibitor of dihydrofolate reductase (DHFR) and therefore also
blocks dTMP production
Term
Sulfonamides (or sulfa drugs)
Definition
antibacterials that compete with paraaminobenzoate in the synthesis of folates in bacteria
Term
OMP decarboxylase
Definition
converts orotidine monophosphate (OMP) to uridine monophosphate (UMP) by liberating carbon dioxide. It is known for being an extraordinarily efficient catalyst
Term
dihydrofolate reductase
Definition
Target of methotrexate. First enzyme involved in regenerating tetrahydrofolate to be used by thymidylate synthase.
Term
Role of Glutamine in acidosis
Definition
Urea cycle decreases, liver glutamine output increases, kidneys take up glutamine and break it down to PEP which is used for gluconeogenesis releasing 2 CO2 and 2 NH3. HCO3- and glucose are released into the blood, protons and NH3 become NH4+ which is excreted in the urine.
Term
Under acidosis what are bicarbonate levels relative to normal?
Definition
decreased
Term
High anion gap
Definition
Elevated anion gap is a sign of acidosis usually caused by an increase in unmeasured anions. Its calculated by subtracting the combined Cl- and bicarb/CO2 concentrations from the Na concentration
Term
exclusive to liver
Definition
Urea cycle, ketone synthesis, fructose catabolism, bile production and bilirubin conjugation, serum protein sythesis
Term
Why do you see an increase in nonesterfied fatty acids in the blood when you have liver damage?
Definition
Decreased gluconeogenisis leads to less insulin signaling so more is released from adipocytes. Also less is taken up by the liver due to the damage.
Term
High Liver NADH leads to increased what? What decreases?
Definition
Increase: Lactic acid, VLDL TG and ketone synthesis. Also hyperuricemia
Decreased: gluconeogenesis, and fatty acid oxidation
Term
Alcohol tolerance is caused by an upregulation of what?
Definition
Cytochrome P450 that is able to oxidize ethanol
Term
Mechanism of hemochromatosis
Definition
Liver is underexpressing Hepcidin
Term
SAM
Definition
S-Adenosyl methionine coenzyme involved in methyl group transfers
Term
Hepcidin
Definition
defensin. secreted from liver. binds ferroportin and causes it to be internalized and degraded. Expression is increased when iron is high or inflammation. decreased when there is anemia or hypoxia.
Term
ceruloplasmin
Definition
Oxidizes Iron to +3 so it can be bound by transferrin in the plasma. Macrophages have a GPI linked ceruloplasmin
Term
Hephaestin
Definition
linked to the basal surface of enterocytes. Oxidizes Iron to +3 so it can be bound by transferrin
Term
Ferroportin
Definition
Ferroportin is a transmembrane protein that transports iron II from the inside of a cell to the outside of it. It is inhibited by hepcidin causing Iron buildup in enterocytes and macrophages
Term
HFE gene
Definition
causes hemochromatosis if mutated
Term
RAD 9
Definition
tumor suppressor that halts cell in G2
Term
MEC1 and ATM
Definition
Tumor supressors that stop cells in the S phase
Term
CDK inhibitors
Definition
make cyclins ineffective until they achieve a high concentration. INK4 during G1. Cip/Kip
Term
WEE1
Definition
inhibitory kinase of CDK
Term
checkpoints work by
Definition
altering the behavior of Cdks, cyclins, and Cdk inhibitors
Term
caffeine and checkpoint control
Definition
stops the checkpoint control that occurs during G2
Term
anaphase promoting complex
(APC)
Definition
responsible for determining when the spindle is complete, then triggering
the dissolution of the chromatid glues that cause anaphase.
Term
Rapamycin
Definition
works by inhibiting mTOR
Term
mTOR
Definition
promotes proliferation. kinase that integrates information from several sources, including a number of tumor suppressor proteins, and is thought to be one of the main sites of integration of information concerning nutrient availability.
Term
survival factors
Definition
All cells have apoptosis as the default action. They are alive only because they are bathed in signals (like IGF and IL-3) telling them not to do it.
Term
FasL or tumor necrosis factor/TNF
Definition
External apoptosis initiation signals. This form of signaling is especially important during the immune response when a cell harboring a pathogen is instructed to die to kill the pathogen.
Term
Bcl-2
Definition
pro-survival (anti-apoptotic) protein. Binds to BAX BID/BAD which would otherwise allow cytochrome C to be released from the mitochondria thus initiating apoptosis. Bcl-2 binding to Apaf-1 directly also prevents apoptosis because it blocks it from binding cyctochrome c
Term
characteristic tests for apoptosis
Definition
flow cytometry: less than 2C DNA content
Agarose Gel: 200 bp latters of DNA (cut at nucleosomes)
TUNEL: Terminal dNTP transferase BrdU
nicked end labeling. number of ends for labeling is greatly increased
Term
phosphatidylserine
Definition
always face cytosol except during apoptosis PS molecules flip to the outer leaflet where they are recognized by PSspecific receptors on phagocytes.
Term
lysoPC
Definition
serves as a chemotactic signal for macrophage recruitment during apoptosis
Term
Ceramide
Definition
Promotes Apoptosis. If its converted to Sphingomyelin than DAG is formed which promotes cell proliferation.
Term
sphingosine-1 phosphate (S1P)
Definition
Metabolite of ceramide. Promotes growth and angiogenisis. lymphocytes exit from lymphoid tissues into blood or lymph in response to S1P gradients
Term
Phosphoinositides role in bacterial invasion.
Definition
Some bacteria are able todo things that change the phosphate arrangements on Phosphoinositides which cause rearrangments of cytoskeleton and allow endocytosis
Term
Phosphoinositides
Definition
Important in growth factor signaling, membrane specification, endocytosis and bacterial invasion. Variation in phosphate position on the head group specifies function
Term
Prpc prion disease infectivity
Definition
Must be on a GIP anchor that allows rapid diffusion and allows it to jump from one cell to another
Term
phospholipase A2
Definition
at the start of synthesizing eicosinoids PA2 first cuts Arachidonic acid from the plasma membrane
Term
COX
Definition
adds 4 oxygens and puts a ring into AA to produces prostaglandins and thromboxanes(cause platelet aggregation). Target of NSAIDS
Term
LOX
Definition
yields the leukotrienes, HETEs, and lipoxins. Does not put a ring in. Important in asthma
Term
conotoxin
Definition
targets Ca channels in neurons
Term
Platelet activating factor
Definition
plasmalogen, ether linked at C1, activates platelets neutrophils and monocytes. Causes leukocytes to adhere and migrate through endothelium.
Term
LCAT and ACAT
Definition
involved in the esterfication of cholesterol. LCAT is in blood and involved with HDLs. ACAT is in cells that store cholesterol for sythesis of steroid hormones.
Term
aromatase
Definition
Enzyme involved in steroid hormone synthesis. Target for drugs that want to prevent ER+ breast cancers
Term
FXR
Definition
Bile acid sensor in enterhepatic system. Low affinity ligand, feedforward regulation.
Term
LXR
Definition
Cholesterol sensor, governs transport, catabolism and elimination of cholesterol. Associated wth Tangier disease and sitosterolemia.
Term
PPARalpha
Definition
involved in fatty acid catabolism
Term
PPARgamma
Definition
promotes fat storage by increasing adipocyte differentiation and transcritpion of lipogenic factors
Term
Apo protein A1
Definition
LCAT cofactor, structural
Term
apo C-II
Definition
lipoprotein lipase cofactor
Term
Apo E
Definition
receptor recognition. involved in retrieval of HDL, VLDL and Chylomicrons
Term
Cholesterol Ester Transfer Protein (CETP)
Definition
catalyzes the transfer of CE from HDL to apo B-containing lipoproteins such as VLDL and LDL
Term
ABCA1
Definition
pumps cholesterol onto HDL particles from peripherial cells. Deficiency leads to tangiers disease, no HDLs
Term
Lipoprotein (a
Definition
the really bad cholesterol
Term
ApoE4
Definition
Poor clinical outcome of Alzheimer strokes and other trauma. ApoE3 is the better form(doesn't form a stable bridge)
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