Flashcards in Final Review Deck (393):
Oxidoreducatase catalyze what reactions?
What class of enzymes are oxidases?
What class of enzymes are oxygenases?
What class of enzymes are reductases?
What class of enzymes are dehydrogenases?
What class of enzymes are kinases?
What class of enzymes are carboxylases?
Transferase and ligases
What class of enzymes are glucokinase
What class of enzymes are glucosidases?
What class of enzymes are ATPases?
What class of enzymes are phosphatases?
What class of enzymes are peptidases?
What class of enzymes are lipases?
What class of enzymes are lyases?
What class of enzymes are mutates?
What class of enzymes are epimerases?
What class of enzymes are racemaces?
What class of enzymes are synthases?
What class of enzymes are synthetases?
What are hydrolases?
cleave bonds by adding water
What are lyases?
Break bonds (usually C-C)
form bonds (need energy input)
What are metalloenzymes?
Enzymes that contain metal
What are prosthetic groups?
Co-enzymes linked to enzymes
What are holoenzymes
Enzyme + prosthetic group
What are apoenzymes?
Enzymes without their prosthetic group
True or false: enzymes increase the forward and reverse reactions by the same amount
What percent of drugs are chiral?
What are three catalytic strategies employed by enzymes?
Acid-base catalysis (show pH optimum)
Formation of covalent bonds
Metal ion catalysis
What are the three ways in which metal ion catalysis works?
1. Stabilize negative charge with metal positive charge
2. generate a Nu by increasing acidity of water/other
3. Bind to substrate
What is specific activity?
U/mg (where U = umol/min)
What is the turnover number?
number of catalytic cycles that one enzyme can perform in one second
Km = ?
Km = (K2+K3)/K1
Aside from the michaelis menton equation what is assumed about Vmax or any V obtained?
Enzyme concentration is constant
true or false Km is independent of [E]?
What is the role of ornithine transcarbomoylase (OTCase) in hyperammonemia?
catalyzes formation of citrulline from carbamoyl phosphate and ornithine (urea cycle)--defects can cause hyperammonemia
What are the effects of a competitive inhibitor on Vmax and Km
Vmax stays the same
What are the effects of a NON-competitive inhibitor on Vmax and Km
Km stays the same
ASA is an irreversible inhibitor of what enzyme? What AA does it form a permantent covalent bond with?
What is the function of vioxx/celebrex?
What is the function of imatinib (Gleevec)?
Inhibits Abl/Bcr tyrosine kinase in chronic myeloid leukemia
How does the poison paranthion work?
Irreversibly binds acetylcholine esterase
What is the function of atropine? When is it administered?
Inhibits bindings of acetylcholine to its receptor
In parathion poisoning
What is the Km of hexokinase? Glucokinase?
0.1 mM, and 5 mM
Where is LDH (lactate dehydrogenase) M found? H?
Muscle = M
Heart = H
What are the two main ways that enzymes may be regulated?
1. change catalytic properties
2. change [E]
What does it mean for an enzymes to be oligomeric?
Controlled by allosteric effectors
How does the attachment of a PO3 2- group to an enzyme affect its activity?
alters conformation by adding bulky group
How is chymotrypsin activated?
How is trypsinogen activated to trypsin?
What are the advantages of multienzyme complexes (3)?
1. eliminate diffusion
2. corrdinated control of steps
3. stichiometric gene expression
The body is made up of about 60% water. What percent is ECF and ICF?
The ECF is composed of interstitial fluid, and plasma. Percentages?
15% interstital fluid
What is the main cation in intracellular fluid?
What is the main anion in intracellular fluid?
PO3 and proteins
What is the main cation of ECF?
What are the main anions of ECF?
Cl and HCO3
Where are carbs found on the plasma membrane?
Outside (or lumens of Golgi)
What is found at C1, C2 and C3 on a phospholipid?
C1 and C2 are FAs. C3 is phosphate
What is phosphatidic acid?
two FAs on glycerol with phosphate (base structure of phospholipids)
What are the three headgroups for a phospholipid discussed in section 1?
What are plasmalogens? Where are they important?
Ether groups attached to glycerol. Myelin sheaths
What is Zwelleger syndrome?
MR d/t lack of peroxisomes needed to produce plasmalogens
What is the polar head group in sphingo lipids? What is connected to the sphingosine backbone via an amide linkage?
What is the effect of an addition of a short chain FA to a phospholipid to the fluidity?
Increases fluidity (less van der waals)
Why are alpha helicies good for membrane spanning proteins?
R groups project outward (can by h-phobic)
What is the difference between a pore and a channel?
Pore have no selectivity except for size, while channels have more selectivity (ion gated, charge etc)
What are gap junctions?
pores between cells that allow for the movement of small molecules
Why are gap junctions important?
Allows for metabolic coordination between cells
What is the protein that makes up connexons?
What type of receptor is the nicotinic-acetylcholine receptor?
ligand gated Na
What is the effect of the nicotinic acetylcholine receptor when acetylcholine binds?
Influx of Na, efflux of K
What allows for the nicotinic acetylcholine receptors specificity?
size, negative charges at the opening
What is myasthenia gravis?
Autoimmune disease that results in muscle weakness due to the attack of nicotinic-acetylcholine receptors
What are the two treatment options for myasthenia gravis?
1. anitcholineesterase (increase [acetylcholine])
2. Immunosuppression drugs
What types of toxins affect the nicotinic acetylcholine receptor?
True or false: facilitated transport displays saturation kinetics and does not use energy
The E1 state of Na/K transporters are opened on what side, and accept what molecule?
cytosolic side, accepts Na
The E2 state of Na/K transporters are opened on what side, and accept what molecule?
ECM side, accepts K
How does Digitalis exert is effects?
inhibit Na/K pumps
Which A.A are never apart of alpha helicies?
P and G
How many AA per turn in alpha helicies?
What does it mean for beta sheet to be parallel?
N termini on side
What are the four classes of cell-signalling molecules?
2. local mediators
4. Growth factors
hydrophilic hormones are generally formed from what? Where do they bind?
Proteins, extracellular plasma membrane
Lipophilic hormones are generally formed from what? Where do they bind?
Inside the nucleus/cytosol
What is the role of pyrophosphatase activity in the adenylate cyclase receptor?
Hydrolyzes the PPi, helping to drive the formation of cAMP
What do the members of the Gs family of proteins activate?
What do the members of the Gi family of proteins participate in?
Inhibit Adenylate cyclase
How is cAMP signalling turned off?
What is the enzymes that degrades glycogen to glucose-1-phosphate?
Through what signalling process does glucagon increase
Gs/ adenylate cyclase--> cAMP-->PKA-->phosphorylase kinase-->glycogen phosphorylase.
What happens to the glucagon receptor after it has bound its receptor?
What is the action of phospholipase C?
convert phosphatidyl inositol to DAG and IP3
What family of G proteins activate phospholipase C?
What does IP3 do?
diffuses to ER--> Ca relase --> activates protein kinase C by bringing it to DAG-->phosphorylation/activation of stuff
What is the effect of calmodulin?
alter activity when bound by Ca
What happens to the IP3 and DAG in the phospholipase C cascade?
DAG is converted to other lipids
What are the three mechanisms that use the phospholipase C pathway?
Alpha 1 androgenic receptors exert their effects through which cascade?
Alpha 2 androgenic receptors exert their effects through which cascade?
Beta 1,2,3 androgenic receptors exert their effects through which cascade?
What is the enzyme and substrate for NO synthesis?
No synthase and R
What is the receptor that activates NO synthase?
Acetylcholine and bradykinin activation calmodulin
What does NO stimulate?
Soluble guanylate cyclase to produce cGMP --> cGMP dependent protien kinase
How do NTG and viagra work?
inhibit cGMP phosphodiesterases
The majority of catalytic receptors are of what type (think insulin receptor)?
protein tyrosine kinases
What is the effect of Atrial naturetic peptides?
bind to guanylate cyclase and stimulate Na and water secretion
What are the primary and secondary responses in lipophilic signalling?
primary is the increased transcription of the targeted molecule
Secondary is an increase in transcription factors that further increases transcription of the target molecule
What is the mechanism behind the cholera toxin?
transfers an ADP-ribose to an R on the Gs protein, keeping it on. (adenylate cyclase on--> CFTR open via phosphorylation)
How does the pertussus toxin in whooping cough exert its effects?
inhibits a Gi protein by adding ADP-ribose to a C residue (stops its inhibition activity)
How does the bubonic plague exert its effects?
Phosphorylates a protein tyrosine kinase in the immune response
What is vitamin B3?
What is vitamin B2?
What are the symptoms and what is the cause of pellagra?
Diarrhea, dementia, dermatitis, and death
The use of bili-lights leads to the destruction of what vitamin?
What makes up CoA (3)?
Vitamin B5 (panntothenic acid)
What are the enzymes used in the PDH complex?
What is the vitamin in the PDH pathway?
Vit B1 (thiamin pyrophosphate; TPP)
Where does the PDH pathway take place?
In the mitochondrial matrix
How does pyruvate get across the mitochondrial membrane?
What are the five coenzymes involved in the PDH complex?
Coa, NAD, TTP, lipoamide and FAD
What are the four B-vitamins in the PDH cycle?
TTP (B1), Riboflavin (B2), niacin (B3), pantothenic acid (B5)
What can defects in the PDH cycle lead to?
Serum lactic acidemia
What are the products of the CAC?
3 NADH, 1 FADH2, and 1 GTP
What are the two ways in which the PDH complex is inhibited?
End porduct inhibition
What are the inhibitors of the PDH cycle for end product inhibition?
Acetyl-coa and NADH
What is the enzyme that phosphoryates the PDH complex to inhibit it?
What are PDH-protein kinase's activators and inhibitors?
A: acetyl-coa, NADH
I: NAD+, CoASH, ADP
What are isocitrate dehydro's activators and inhibitors?
What are aKG's inhibitors?
I: succinyl-CoA, NADH
What are the symptoms of Thiamin deficiency?
Pellegra/acidemia due to inhibition of PDH
What is beri-beri?
Severe thiamin deficiency present like pellegra/acidemia
Which is more permeable, the inner or outer mt membrane? Why?
Outer--has less proteins than the inner (inner is 80% protein, 20% lipids, 50/50 for outer)
What are the four types of dehydrogenases in the ETC?
Fatty acid dehydro
True or false, the Fe in the cytochrome proteins can undergo oxidation from the Fe2+ to Fe 3+
What is the only non-protein electron carrier in the ETC?
Co-Q (it's a lipid)
What is the name of complex 1?
What is the name of complex II?
What is the name of complex III?
CoQH2 -cytochrome C reductase
What is the name of complex IV?
Where do cyanide and CO inhibit the ETC?
What is the election donor to complex II?
Succinate (note that this initial rsn is not enough energy to generate an ATP, thus only 2 ATP are produced)
What are the two subunits of ATP synthase, and what are their functions?
F0 = channel
F1 = actual functional part of the cell
How does DNP work?
Uncouples the [H] gradient by bringing protons across the membrane and releasing them
What is the biological uncoupling protein discussed in class?
What is the function of atractyloside?
Inhibits mt ATP translocase
What is Leber's hereditary optic neuropathy?
sudden onset blindness d/t mt mutation for complex I
What is Myoclonic Epilipsey and ragged red fibers (MERRF)?
Abnormal skeletal muscle shape due to mt containing paracrystalline array.
Cytochrome oxidase activity is diminished d/t tRNA mutation
What is mitochondrial encephalopathy, lactic acidosis, stroke-like activty (MELAS)?
Point mutation in tRNA producing ragged red fiber but cytochrome oxidase activity is NORMAL
What is the action of DNP derivatives?
What is the action of cyanide?
Blocks complex IV
What is the treatment for cyanide poisoning?
nitrates and ferric Fe (to cause cyanide to bind to Hb rather than cytochrome)
What is the purpose of adding carbs to proteins?
What is mutorotation in terms of carbs?
Switching between the alpha and beta forms in free solution
in alpha glucose, is the C1 OH group on the same or opposite side as C6?
in beta glucose, is the C1 OH group on the same or opposite side as C6?
same side as C6
What are advanced glycosylation end products?
highly reactive glycosylated chemicals
Reduction of glucose leads to the formation of what two products?
Sorbitol and inostiol
What is the isoform of hexokinase in the liver called?
What is the purpose of adding sulfur to carbs?
Needed for ECM production (adds a negative charge as well)
What does it mean to activate a sugar?
Transfer it to an nucleotide trisphosphate
What are the enzymes that form glycosidic bonds?
Maltose is a disacharride of what two molecules?
lactose is a disacharride of what two molecules?
Galactose and glucose
Sucrose is a disacharride of what two molecules?
Glucose and fructose
Why is sucrose less reactive than other disacharides?
no free reducing end
Amylose and amylopectin are polymers of what molecule?
Cellulose has what kind of glucose bonds?
What is the difference between amylopectin and glycogen?
More branching on glycogen
What is the function of GAGs in animals?
What is the enzyme that breaks beings the breakdown of starch/glycogen in the saliva? What are the main products?
Maltose and maltotrioses
sucrose is degraded by what enzyme in the gut?
What are the next two enzymes that break down the porducts of alpha amylase?
isomaltase and glucosidase
Where does SGLT 1 get its energy from?
Where is GLUT 1 found? What does it do?
Everywhere, basal glucose uptake
GLUT2 does what?
removes glucose from liver, intestine, gives to blood
What does GLUT3 do?
basal glucose uptake
what does GLUT 4 do?
INDUCIBLE BY INSULIN
muscle and adipose tissue gluc uptake
What does GLUT 5 do?
Uptake fructose in liver. NOT affected by insulin
What cells produce fructokinase?
What is the cause of fructosuria? Is this severe?
What is the cause of heriditary fructose intolerance? Symptoms?
Aldolase B defect.
Accumulates fructose-1-phosphate in liver, phosphate pools drained
What are the three causes of galactosemia?
1. Defect galactokinase
2. Defect in galactose-1-phosphate uridyltransferase
3. Defect in UDP galactose epimerase
What are the three regulated enzymes in glycolysis?
What stimulates/inhibits hexokinase
I: G6P, acetyl-coa,
What stimulates/inhibits PFK I?
S: ADP, AMP, F(2,6)bisphosphate
I: ATP, citrate
What stimulates/inhibits Pyruvate kinase?
S: fructose 1,6, bisphosphate, insulin
What are the two mitochondrial shuttle mechanisms for transporting NADH? Where are they found?
Glycerol phosphate in muscles and brain
Malate-D shuttle in liver and heart
What is the essential enzyme in the Cori cycle?
What happens in pyruvate kinase deficiency?
Pyruvate--> lactate, lactic acidemia
How does arsenic exert its effects?
Takes the place of phosphate in rxn from G3P to 1,3 BPG.
Can FAs be used to generate glucose?
Where does the conversion of pyruvate to OAA occur?
Where does the conversion of OAA to PEP occur?
mito or cyto
What is the hormone that mothers produce that stimulates milk production?
Glucose-6-phosphate dehydro is regulated how?
Inhibited by NADPH
Deficiency of Glucose-6-phosphate dehydrogenase leads to what disease? What are they sensitive to?
G6PD deficiency = sensitivity to H2O2, fava beans, infection
What is glycogenin?
The substance that glycogen is synthesized on
Why don't muscles respond to glucagon?
They lack glucose-6-phosphatase
Does phosphorylation favor glycogen creation or degadation? (e.g is glycogen phosphorylase active in the phosphorylated state or not)
Phosphorylation of glycogen synthase does what (inactivates or activates it)?
Phosphorylation of glucose-6-phosphatase does what (inactivates or activates it)?
What is the action of protein phosphatase 1 (PP1) in the liver? What is it stimulated by?
Stimulated by insulin, and dephosphorylates all of the proteins in the liver that were phosphorylated by PKA
What is van gierke's disease?
defect in glucose-6-phosphatase. leads to increased liver stores
What is Pompe's disease?
Defiecicncy in acid maltase (alpha-glucosidase) that is present in lysosomes. Lysomal glycogen accumulates
What is cori disease?
Defect in the glycogen debranching enzyme
What is McArdles disease?
defect in glycogen phosphorylase, muscles cannot use glycogen
What are the two pathways that alcohol is metabolized?
Via p450 or by two enzymes (alcohol dehydo, + aldehyde dehydro)
What molecule does the metabolism of EtOH produce, and what is the effect on the CAC, lactate production, and FA synthesis?
NADH, inhibits CAC and lactate
Increases FA synthesis
Where does protein glycosylation (the process of it) take place?
Golgi and ER
What are the two Amino acids that are used to attach carbs to?
S and N
The monomeric units for the synthesis of glycosaminoglycans
activated sugar molecules
What is the enzyme that adds sulfur groups to GAGs?
Proteoglycans are degraded in what?
What is the defective enzymes in hunter syndrome? What accumulates?
Iduronate sulfatase deficiency causes dermatan and heparan sulfate to accumulate
What is the defective enzymes in Hurler syndrome? What accumulates?
Alpha-Iduronate sulfatase deficiency causes dermatan and heparan sulfate to accumulate
What reaction does the enzyme UGT catalyze?
Addition of UDP glucose to xenobiotics
Up to what carbon number can the body synthesize unsaturated FAs?
What are the two essential FAs?
Linoleic and Linolenic acid
What are the three enzymes involved in carnitine transport?
Defects in Carnitine transport (primary carnitine deficiency) leads to what physiological state?
If a double bond occurs between carbon 3 and 4 of a FA, what enzyme converts the cis-3 double bond into the trans-delta2-enoyl CoA (which is part of the Beta FA oxidation chain)?
If a double bond of a FA occurs between carbon 4 and 5 of the FA chain, what enzyme converts it to a tran-delta- 3 bond? What enzyme will then convert it to a trans-delta-2 bond?
Where does beta-oxidation occur in the cell?
Mitochondria, some in peroxisomes
What are the two differences between beta oxidation in peroxisomes, and the same process in mitochondira?
1. initial oxidation of Fatty-acyl group produces H2O2, rather than FADH
2. Peroxisomal degradation degrades LCFAs, and ends when they are shortened to 8 carbons
What is actue fatty liver of pregnancy?
Deficiency of LCFA dehydrogenase
Acyl-Coa dehydrogenase deficiencies present as what?
Non-ketotic fasting hypoglycemia
What is Refsum disease?
problem with digesting phytanic acid (metabolite of chlorophyll). Results in neurological defects
Where is the enzyme HMG-CoA lyase expressed. Why is this important?
Liver and kidneys
Important so that only these two organs make ketone bodies
What is the enzyme that is expressed outside the liver and kidneys, and begins the process of breaking down the beta-hydroxybutryate produced by ketone body metabolism?
For every turn of the FA synthesis cycle, how many NADPHs are used?
Where does the elongation of FAs occur?
Mito or ER
How does elongation of FAs occur in the the ER?
Similar to FA synthase
How does elongation of FAs occur in the mito?
reverse beta oxidation
True or false: lipid droplets are stored surrounded by a lipid bilayer, which has perilipin and lipases in it
False--monolayer. O/w true
What is the glyoclytic intermediate for glycerol?
What is the enzymes that converts DHAP to glycerol or v.v.?
Glycerol phosphate dehydrogenase (note, glycerol, not glyceraldehyde)
What are the two enzymes involved in the synthesis of TAGs? What is the substrate they act on?
Glycerol 3 phosphate
Insulin induces the expression of 4 enzymes involved in FA synthesis. What are they?
1. FA synthase
2. Malic Enzyme
3. glucose-6-phosphate dehydrogenase
4. acetyl-coa carboxylase
Insulin activates a FA synthesis enzyme, as well as another process through phosphorylation. What are these two things?
1. FA synthase
2. Glycolysis (though hexokinase, and pyruvate kinase)
Why does the level of FA synthesis fall when insulin goes down and glucagon goes up?
1. insulin no longer present to stimulate
2. Phosphorylation of enzymes by AMPK (such as acetyl-CoA carboxylase)
How does malonyl CoA inhibit FA degradation?
Inhibits CPT I
How is the release of FAs regulated?
1. Glucagon/adenylate cyclase/cAMP/PKA phosphorylates hormone sensitive lipase and perilipin.
2. Decreased malonyl-CoA means CPT I is no longer inhibited
The amount of FAs released during starvation far exceeds the need. What happens to these FAs?
Reesterified and packed into LDL by liver, recycled back to adipose tissue
Phosphatidyl choline can be synthesized via an activated nucleotide (CTP), as well as phosphocholine. What is the enzyme that activates the phosphocholine? What happens next?
DAG is transferred to the activated CDP-choline via choline phosphotransferase
What is the enzyme that synthesizes phosphatidyl serine from phosphatidyl ethanolamine?
What is the enzyme that synthesizes phosphatidyl choline from phosphatidyl ethanolamine?
Phosphatidylethanolamine N methyltransferase
Why is the synthesis of phosphatidyl inositol different from the synthesis of the rest of the lipids?
Uses activated DAG rather than an activated head group
For the synthesis of membrane lipids, what is the general outline of the reaction?
1. Activation of the head group by transferring a CTP group to produce CDP-head group
2. Transferring the activated head group to DAG
What is the enzyme that catalyzes the synthesis of phosphatidyl inositol from inositol and an activaed DAG?
Phosphatidyl inositol synthase
What is cardiolipin? What role does it play?
Two DAGs attached to one another via a methyl linkage
Helps with folding of mito ETC
What is the role of phospholipase A1 and A2? what about Phospholipase C?
Phospholipase A1 and A2 removes FAs on C1 and C2 of DAG respectively..
Phospholipase C removes C3
Why are phospholipases important?
Allow for modification of newly synthesized lipids
What is the enzyme that synthesizes PGG from arachiodonic acid?
What is the enzyme that takes PGG produced from COX1/2 and turns it into PGH?
What is the enzyme that synthesizes thromboxane? What is the precursor?
What is the enzyme that starts arachidonic acid down the pathway of leukotriene synthesis?
What is the target for asthma drugs that stops the production of leukotrienes?
Where does the synthesis of plasmalogens take place?
What are the amino acid and FA used to synthesize ceramide, the precursor for sphingolipids?
Serine + Palmitoyl-CoA
The transfer of phosphocholine to ceramide yields what?
The transfer of glucose/galactose to ceramide yields what?
The transfer of suflate to cerbrosides yields what?
The transfer of 2-4 neutral sugars to ceramide yields what?
The transfer of NANA to ceramide yields what?
What is the enzyme defect in Gaucher's disease, and what accumulates?
Beta-glucosidase, accumulates glucocerebroside. Leads to hepatosplenopmegaly
Where is the cell does cholesterol synthesis occur?
What can Farnesyl be used for, besides cholesterol synthesis?
prenylation of proteins
element of CoQ
Two farnesyls combine to form what? What comes from this?
What are the three ways in which HMG reductase is regulated?
Insulin dephos it
Cholesterol inhibits it
What is the target of Statins?
What is the enzyme that esterifies cholesterol?
What enzymes breaks down cholesterol?
Humans lack this enzyme
How do insulin, cortisol, and glucagon affect HSL?
Insulin inhibits it
Glucagon stimulates it
Cortisol induces it
What are the four apoproteins?
Apoprotein A, B, C, and E
What is the function of apoprotein A?
Have LCAT, and will extract lipids from cells
What is the function of apoprotein B?
Structural and receptor
What is the function of apoprotein C?
Modulate function of lipoprotein lipase
Liberate fatty acids and release them to cells
What is the function of apoprotein E?
Apoprotein B48 is found where?
What are the two reasons for hyperlipidemia observed in pts with DM?
Overactive hormone sensitive lipase
Inactive lipoprotein lipases (part of LDL)
What is the defective/deficient enzyme in Tyrosinemia I?
Tyrosine amino transferase
What is the defective/deficient enzyme in Tyrosinemia II?
What is the defective/deficient enzyme in alkaptonuria?
What is the defective/deficient enzyme in homocysteine uria?
Why must [K] be monitored closely in DM II pts?
Because K is lost in polyuria, and is taken in with insulin administration
What are the three major consequences of uncontrolled DM?
What is the signal for the release of insulin?
ATP, causes the release of Ca
What are the two important enzymes the insulin increses the transcription of?
What is the one important enzyme that insulin decreases the transcription of?
Why does EtOH exacerbate porphyrias?
Increases heme synthesis for the p450 enzymes
WHat is AIP (acute intermittent porphyria?)
Defeciency in porphobilinogen deaminase
What is the cause of prophyria cutanea tarda?
Deficiency of uroporphyrinogen, leads to build up of UPG III
What part of the heme synthesis pathway does Pb inhibit?
ferrochelatase and PBG synthase
What is the difference between direct and indirect bili?
Direct = water soluble
Indirect = not so much
What type of bili is excreted in the urine? In the feces?
Urobiliogen in the feces
Urobilin in the urine
What are the the causes of prehepatic jaundice?
What are the defining features of prehepatic jaundice vs hepatocellular jaundice vs cholestatic jaundice?
1. Prehepatic has elevated indirect bili
2. Hepatocellular has high indirect in serum, and ALT + AST. (Pale feces also)
3. Cholestatic jaundice has intense urine color (and direct bili)
What are the two inhibitors of PRPP synthetase?
ADP and GDP
What are the two inhibitors of amidoribosyltransferase?
AMP and GMP
What is hyperuricemia?
Excess uric acid in the blood due to reduced excretion or increased production of uric acid
HOw does EtOH consumption increase the effects or uric acid?
decreased excertion of uric acid, and increased production
What is the action of allopurinol?
Decrease the production of uric acid, by inhibiting xanthine oxidase
What is orotic acid uria?
Defect in UMP synthease (leads to megaloblastic anemia)
What is the enzyme that catalyzes CTP from UTP?
What is the enzyme that regulates pyrimidine synthesis?
Carbamoyl phosphate synthase II
Where are the inhibitors/activators of carbamoyl phosphate synthetase?
Inhibited by UTP and activated by PRPP
What is the enzyme that catalyzes the production of dNDPs from NDP
What is the chemical that is reduced i the ribonucleotide ruductase reaction? What is the electron donor that regenerates this?
NADPH (via thioredoxin reductase)
SCID can be caused by a deficiency of what?
What is the effect of hydroxyurea on ribonucleotide reductase?
What is the enzyme that converts dUMP to dTMP? What other substrate is needed for this reaction?
N5N10 methylne THF (goes to dihydrofolate)
What is the action of 5-flurouracil?
COonverted to FUMP, and inhibits thymidlyate synthatse
Degradation of pyrimidine nucleotides yields what?
beta-alanine, except for dTMP
Degradation of dTMP laeds to what?
What are the two enzymes the are needed for purine salavege?
HGPRTase (forganin and hypoxanthine)
APRTase for Adendine
How are HGPRTase and APRTase regulated?
How do the salvage pathways inhibit de novo syntehsis?
Take up PRPP and incrased AMP/GMP withich inhibit amidophosphpribosltrasferase
What is the only purine nucleoside that can be taken up by humans directly?
What is the cause of Lesc-Nyhan syndrome?
Deficiency of HGPRTase--leads to MR
What is the enzyme that allows for the uptake or pyrimidine uptake? What pyrimidine cannot be taken up?
What is the two ways in which cytochrome p450 induces liver damage?
Generation of a hydroxyethyl radical
Whatr is the function of superoxide dismutase?
Takes 2O2- and reduces it to hydrogen peroxide
What is the function of catalase?
Detoxifies hydrogen peroxide by converting it into water
What is the function of Glutathinoe peroxidase?
takes hydrogen peroxide and reduces it to water
What are the three vitamins that play a role in antioxidation?
Vit A, C, E
What are the two enzymes that are involved in glutathione oxidation/reduction? What does the reduction of glutathinoe require?
Glutathinoe peroxidase and reductase
Reduction needs NADPH
What is the ultimate source electrons for the reduction of radicals?
What is the function of methhb?
Repairs Fe 3+ to Fe2+, whose oxidation is the result of hydrogen peroxide
What is the only way that malondialdehyde is produced?
From the hydroxy radical reaction of PUFAs
What are the three steps of membrane damage via radicals?
1. Radical formed when OH radical attacks unsaturated bond of PUFA.
2. Oxygen reacts with the lipid radical, which will then extractelectrons from eighter itself (malondialdehyde) or other FAs. This lead to propagation
What role do disulfide birdfges play in free radicals?
sulfide bridges are a site of ROS interaction, and modification of these sites can lead to incorrect bond formation and breakage
What does most of the satillite DNA acount for?
centromeres and telomeres
What are pseudogenes?
Duplicated genes that have been inactivated
Palindromic sequences of DNA nucleotides create what type of structure/.
Long runs of pryimidine/purine nucleotides create what type of structure?
What is the target of naldixic acid and cipro?
Target prokaryotic topoisomerase II
Incorrect recombination where unequal corssover occurs is more likely to happen where on the chromosomes (think base pairs)?
Where there are large, repetitive sequences
Where do strand slippages occur?
Sequences of repeats, such that the DNA can loop back on itself
What are chiasmata?
Sites of chromosomal crossover
What is a genome mutation?
Change in the number of chromosomes
HNPCC (lynch syndrome) is the result of what?
Mutations in the DNA mismatch repair mechanism
What is the role of DNA glycosylases?
Recognize specific DNA mismatches and remove them
When is DNA base excision repair used? Nucleotide excision repair?
Base is just for point mutations
Nucleotide is when there are thymine dimers
What are the four steps of base excision repair?
1. glycosylase remove base
2. AP endonuclease clips phosphodiester back bone
3. DNA phosphodiesterase removes phosphoribose
4. DNA polymerase/ligase repair
What are the two steps of nucleotide excision repair?
1. nucleases and helicases remove large chuck of DNA around the dimer
2. DNA pol delta and DNA ligase repair it
What is the cause of xeroderma pigmentosum?
Defect in nucleotide excision repair
What is cytarabine, and how does it work?
Cytidine analog that has arabinose instead of ribose
converted to cytarabine trisphosphate in the cells and compete with dNTPs for binding with DNA polymerases
What is cyclophosphamide what what does it do?
Cyclic drug that turns into phosphoramide mustard and cuases DNA strand links
What does SP1 (the general promoter protein) bind to?
GC rich regions box
What does the general promotor protein NF1 bind to?
What is the effect of the death cap mushroom?
Inhibits Pol II. Liver failure
What is the action of Rifampicin?
Inhibits RNA polymerase II in TB
What is the base that begins the process of splicing?
What is the polyadenylation signal?
DNA sequence that direct the application of a 3' tail
What is the genetic problem in beta thalessemia?
mutation in the Beta-globin gene splice site
What is the genetic basis for PKU?
mutation in the 5' splice site
SRE1 is a transcription binding protein for what pathway?
What does the protein CRSP do?
binds to SP-1 in the LDL transcription complex
What is the function of SREBP1?
Maintained outside of the nucleus, and will go into the nucleus in response to low cholesterol levels. Binds to SRE.
Where is the cortisol receptor located? What keeps it there? What does it bind to?
located in the cytoplasm, where it is masked by several proteins. Binding of cort will transduce it to the nucleus, where it will bind GRE.
What are the two proteins whose transcription is induced by cort binding to the cortisol receptor?
What is bound to the thyroid receptor in the nucleus?
What is rubinstein-taybi syndrome?
Mutated EP300/CBP proteins, which does not allow for the binding to CRE, and diminished PEP carboxykinase to be produced
How does PKA induce the transcription of PEP carboxykinase?
PKA phosphorylates CREB, which binds CBP and the CRE promoter element. CRE recruits EP300 and functions as a HAT.
What is the action of tamoxifen?
Competitive inhibitor of the estrogen receptor
What is ataxia teleangiectasia?
Inhibition of of ATM, leading to easily developing lymphomas and leukemias
What is the role of Apaf?
Forms that flower thingy in response to cytochrome C and bax activation, and leads to the stimulation of caspase 9-->3
What are the six changes that need to occur for cell to become a metastatic cancer?
1. Self-sufficiency in growth signals
2. Insensitivity to antigrowth signals
3. Evade apoptosis
4. Limitless replicative potential
5. Sustained angiogenesis
6. Tissue invasion and metastasis
Ras mutations are particularly prominent in what type of cancers?
What is Burkett's lymphoma?
Due to the translocation of a c-myc gene from chromosome 8 to 14. B cells become cancerous
Retinoblastoma is the result of what?
Mutation in RB1 gene. Follows two hit model
What is the protine that associates with p53 and causes its instability?
Why is it significant that p53 functions as a homotetramer?
One change leads to dysfunctions protein
What is Li-Fraumieni syndrome?
mutation in p53, leading to a crap ton of cancers
What is the function of neurofibromin?
Accelerates that degradation of neurofibromin
What are the two proteins that are involved in HPV? What do they inhibit?
E6 inhibits p53
E7 inhibits Rb
What do the BRCA1/2 genes do?
Involved in DNA double stranded repair and getting proteins to the sites of repair
What is the protein that is involved in angiogenesis of tumor cells?
How is HIF-1alpha-beta stimulated?
hypoxia will inhibit a proline hydroxylase (which coordinates with VHL protein) that causes the polyubiquitination of the HIF1alpha-beta protiein
What are the proteins that usually hold epithelial cells together?
What are the enzymes that tumor cell overexpress and lead to intravasation?
Matrix metalloproteases (MMPs)
What is Familial adenomatous polyposis (FAP)?
A condition where thousands of polyps are found in the intestines. Due to a mutation in the APC gene
What pathway is the APC gene involved in (in FAP)?
What is the protein in the WNT pathway that actually stimulates transcription?
What does Beta-catenin stimulate specifically?
Nyc and Cyclin D
How does the APC protein regular the beta-catenin protein?
Forms a destruction complex normally, unless a signal is received.
What are the genes that are mutated in HNPCC? What do each of these do?
MSH2 - identifies DNA mismatches
MLH1 - repairs DNA mismatches
A reciprocal translocatio between chromosomes 9 and 22 is indicative of what disease? What is the new protein produced?
Chronic myeloid leukemia
Bcr/Abl Tyrosine kinase
What is the function of imatinib mesylate (Gleevec)?
Inhibits the Y-kinase of Bcr/Abl1 mutation of the Philadelphia chromoesome of chronic myeloid leukemia
What is the function of herceptin (Trastuzumab)?
Inhibits the HER2/Neu receptor