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Flashcards in Final Review Deck (393):
1

Oxidoreducatase catalyze what reactions?

Redox

2

What class of enzymes are oxidases?

Oxidoreductases

3

What class of enzymes are oxygenases?

Oxidoreductases

4

What class of enzymes are reductases?

Oxidoreductases

5

What class of enzymes are dehydrogenases?

Oxidoreductases

6

What class of enzymes are kinases?

Transferase

7

What class of enzymes are carboxylases?

Transferase and ligases

8

What class of enzymes are glucokinase

Transferase

9

What class of enzymes are glucosidases?

Hydrolase

10

What class of enzymes are ATPases?

Hydrolase

11

What class of enzymes are phosphatases?

Hydrolase

12

What class of enzymes are peptidases?

Hydrolase

13

What class of enzymes are lipases?

Hydrolase

14

What class of enzymes are lyases?

Lyases

15

What class of enzymes are mutates?

isomerases

16

What class of enzymes are epimerases?

isomerases

17

What class of enzymes are racemaces?

isomerases

18

What class of enzymes are synthases?

ligase

19

What class of enzymes are synthetases?

ligase

20

What are hydrolases?

cleave bonds by adding water

21

What are lyases?

Break bonds (usually C-C)

22

isomerases ligases?

form bonds (need energy input)

23

What are metalloenzymes?

Enzymes that contain metal

24

What are prosthetic groups?

Co-enzymes linked to enzymes

25

What are holoenzymes

Enzyme + prosthetic group

26

What are apoenzymes?

Enzymes without their prosthetic group

27

True or false: enzymes increase the forward and reverse reactions by the same amount

True, always

28

What percent of drugs are chiral?

50%

29

What are three catalytic strategies employed by enzymes?

Acid-base catalysis (show pH optimum)
Formation of covalent bonds
Metal ion catalysis

30

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

31

What is specific activity?

U/mg (where U = umol/min)

32

What is the turnover number?

number of catalytic cycles that one enzyme can perform in one second

33

Km = ?

Km = (K2+K3)/K1

34

Aside from the michaelis menton equation what is assumed about Vmax or any V obtained?

Enzyme concentration is constant

35

true or false Km is independent of [E]?

true

36

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

37

What are the effects of a competitive inhibitor on Vmax and Km

Vmax stays the same
Km increases

38

What are the effects of a NON-competitive inhibitor on Vmax and Km

Vmax decreases
Km stays the same

39

ASA is an irreversible inhibitor of what enzyme? What AA does it form a permantent covalent bond with?

Prostaglandin synthetase
S

40

What is the function of vioxx/celebrex?

inhibit COX-2

41

What is the function of imatinib (Gleevec)?

Inhibits Abl/Bcr tyrosine kinase in chronic myeloid leukemia

42

How does the poison paranthion work?

Irreversibly binds acetylcholine esterase

43

What is the function of atropine? When is it administered?

Inhibits bindings of acetylcholine to its receptor

In parathion poisoning

44

What is the Km of hexokinase? Glucokinase?

0.1 mM, and 5 mM

45

Where is LDH (lactate dehydrogenase) M found? H?

Muscle = M
Heart = H

46

What are the two main ways that enzymes may be regulated?

1. change catalytic properties
2. change [E]

47

What does it mean for an enzymes to be oligomeric?

Controlled by allosteric effectors

48

How does the attachment of a PO3 2- group to an enzyme affect its activity?

alters conformation by adding bulky group

49

How is chymotrypsin activated?

By trypsin

50

How is trypsinogen activated to trypsin?

Enteropeptidase

51

What are the advantages of multienzyme complexes (3)?

1. eliminate diffusion
2. corrdinated control of steps
3. stichiometric gene expression

52

The body is made up of about 60% water. What percent is ECF and ICF?

ECF =20%
ICF=40%

53

The ECF is composed of interstitial fluid, and plasma. Percentages?

5% plasma
15% interstital fluid

54

What is the main cation in intracellular fluid?

K+

55

What is the main anion in intracellular fluid?

PO3 and proteins

56

What is the main cation of ECF?

Na

57

What are the main anions of ECF?

Cl and HCO3

58

Where are carbs found on the plasma membrane?

Outside (or lumens of Golgi)

59

What is found at C1, C2 and C3 on a phospholipid?

C1 and C2 are FAs. C3 is phosphate

60

What is phosphatidic acid?

two FAs on glycerol with phosphate (base structure of phospholipids)

61

What are the three headgroups for a phospholipid discussed in section 1?

Ethanolamine
Phosphatidyl serine
Phosphatidyl inositol

62

What are plasmalogens? Where are they important?

Ether groups attached to glycerol. Myelin sheaths

63

What is Zwelleger syndrome?

MR d/t lack of peroxisomes needed to produce plasmalogens

64

What is the polar head group in sphingo lipids? What is connected to the sphingosine backbone via an amide linkage?

Phosphoryl choline.
a FA

65

What is the effect of an addition of a short chain FA to a phospholipid to the fluidity?

Increases fluidity (less van der waals)

66

Why are alpha helicies good for membrane spanning proteins?

R groups project outward (can by h-phobic)

67

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)

68

What are gap junctions?

pores between cells that allow for the movement of small molecules

69

Why are gap junctions important?

Allows for metabolic coordination between cells

70

What is the protein that makes up connexons?

Connexin

71

What type of receptor is the nicotinic-acetylcholine receptor?

ligand gated Na

72

What is the effect of the nicotinic acetylcholine receptor when acetylcholine binds?

Influx of Na, efflux of K

73

What allows for the nicotinic acetylcholine receptors specificity?

size, negative charges at the opening

74

What is myasthenia gravis?

Autoimmune disease that results in muscle weakness due to the attack of nicotinic-acetylcholine receptors

75

What are the two treatment options for myasthenia gravis?

1. anitcholineesterase (increase [acetylcholine])
2. Immunosuppression drugs

76

What types of toxins affect the nicotinic acetylcholine receptor?

alpha-neurotoxins

77

True or false: facilitated transport displays saturation kinetics and does not use energy

True

78

The E1 state of Na/K transporters are opened on what side, and accept what molecule?

cytosolic side, accepts Na

79

The E2 state of Na/K transporters are opened on what side, and accept what molecule?

ECM side, accepts K

80

How does Digitalis exert is effects?

inhibit Na/K pumps

81

Which A.A are never apart of alpha helicies?

P and G

82

How many AA per turn in alpha helicies?

3.6

83

What does it mean for beta sheet to be parallel?

N termini on side

84

What are the four classes of cell-signalling molecules?

1. Hormones
2. local mediators
3. Neurotransmitters
4. Growth factors

85

hydrophilic hormones are generally formed from what? Where do they bind?

Proteins, extracellular plasma membrane

86

Lipophilic hormones are generally formed from what? Where do they bind?

cholesterol
Inside the nucleus/cytosol

87

What is the role of pyrophosphatase activity in the adenylate cyclase receptor?

Hydrolyzes the PPi, helping to drive the formation of cAMP

88

What do the members of the Gs family of proteins activate?

Adenylate cyclase

89

What do the members of the Gi family of proteins participate in?

Inhibit Adenylate cyclase

90

How is cAMP signalling turned off?

cAMP phosphodiesterases

91

What is the enzymes that degrades glycogen to glucose-1-phosphate?

Glycogen phosphorylase

92

Through what signalling process does glucagon increase

Gs/ adenylate cyclase--> cAMP-->PKA-->phosphorylase kinase-->glycogen phosphorylase.

93

What happens to the glucagon receptor after it has bound its receptor?

Degraded

94

What is the action of phospholipase C?

convert phosphatidyl inositol to DAG and IP3

95

What family of G proteins activate phospholipase C?

Gq

96

What does IP3 do?

diffuses to ER--> Ca relase --> activates protein kinase C by bringing it to DAG-->phosphorylation/activation of stuff

97

What is the effect of calmodulin?

alter activity when bound by Ca

98

What happens to the IP3 and DAG in the phospholipase C cascade?

kinased/phosphatased away
DAG is converted to other lipids

99

What are the three mechanisms that use the phospholipase C pathway?

PDGF
Oxytocin
Epi

100

Alpha 1 androgenic receptors exert their effects through which cascade?

Gq

101

Alpha 2 androgenic receptors exert their effects through which cascade?

Gi

102

Beta 1,2,3 androgenic receptors exert their effects through which cascade?

Gs

103

What is the enzyme and substrate for NO synthesis?

No synthase and R

104

What is the receptor that activates NO synthase?

Acetylcholine and bradykinin activation calmodulin

105

What does NO stimulate?

Soluble guanylate cyclase to produce cGMP --> cGMP dependent protien kinase

106

How do NTG and viagra work?

inhibit cGMP phosphodiesterases

107

The majority of catalytic receptors are of what type (think insulin receptor)?

protein tyrosine kinases

108

What is the effect of Atrial naturetic peptides?

bind to guanylate cyclase and stimulate Na and water secretion

109

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

110

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)

111

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)

112

How does the bubonic plague exert its effects?

Phosphorylates a protein tyrosine kinase in the immune response

113

What is vitamin B3?

Niacin

114

What is vitamin B2?

Riboflavin

115

What are the symptoms and what is the cause of pellagra?

Niacin deficiency,
Diarrhea, dementia, dermatitis, and death

116

The use of bili-lights leads to the destruction of what vitamin?

B2

117

What makes up CoA (3)?

AMP
Vitamin B5 (panntothenic acid)
Mercaptoethylamine

118

What are the enzymes used in the PDH complex?

Pyruvate decarboxylase
dihydrolipoyl tranacetylase
Dihydrolipoyl dehydrogenase

119

What is the vitamin in the PDH pathway?

Vit B1 (thiamin pyrophosphate; TPP)

120

Where does the PDH pathway take place?

In the mitochondrial matrix

121

How does pyruvate get across the mitochondrial membrane?

translocase

122

What are the five coenzymes involved in the PDH complex?

Coa, NAD, TTP, lipoamide and FAD

123

What are the four B-vitamins in the PDH cycle?

TTP (B1), Riboflavin (B2), niacin (B3), pantothenic acid (B5)

124

What can defects in the PDH cycle lead to?

Serum lactic acidemia

125

What are the products of the CAC?

3 NADH, 1 FADH2, and 1 GTP

126

What are the two ways in which the PDH complex is inhibited?

End porduct inhibition
Phosphorylation

127

What are the inhibitors of the PDH cycle for end product inhibition?

Acetyl-coa and NADH

128

What is the enzyme that phosphoryates the PDH complex to inhibit it?

PDH-protein kinase

129

What are PDH-protein kinase's activators and inhibitors?

A: acetyl-coa, NADH
I: NAD+, CoASH, ADP

130

What are isocitrate dehydro's activators and inhibitors?

A: ADP
I: NADH

131

What are aKG's inhibitors?

I: succinyl-CoA, NADH

132

What are the symptoms of Thiamin deficiency?

Pellegra/acidemia due to inhibition of PDH

133

What is beri-beri?

Severe thiamin deficiency present like pellegra/acidemia

134

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)

135

What are the four types of dehydrogenases in the ETC?

Succinate dehydro
NADH dehydro
Fatty acid dehydro
G3P dehydro

136

True or false, the Fe in the cytochrome proteins can undergo oxidation from the Fe2+ to Fe 3+

true

137

What is the only non-protein electron carrier in the ETC?

Co-Q (it's a lipid)

138

What is the name of complex 1?

NADH-CoQ reductase

139

What is the name of complex II?

Succinate-CoQ reductase

140

What is the name of complex III?

CoQH2 -cytochrome C reductase

141

What is the name of complex IV?

Cytochrome oxidase

142

Where do cyanide and CO inhibit the ETC?

Complex IV

143

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)

144

What are the two subunits of ATP synthase, and what are their functions?

F0 = channel
F1 = actual functional part of the cell

145

How does DNP work?

Uncouples the [H] gradient by bringing protons across the membrane and releasing them

146

What is the biological uncoupling protein discussed in class?

Brown fat

147

What is the function of atractyloside?

Inhibits mt ATP translocase

148

What is Leber's hereditary optic neuropathy?

sudden onset blindness d/t mt mutation for complex I

149

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

150

What is mitochondrial encephalopathy, lactic acidosis, stroke-like activty (MELAS)?

Point mutation in tRNA producing ragged red fiber but cytochrome oxidase activity is NORMAL

151

What is the action of DNP derivatives?

Uncouple ETC

152

What is the action of cyanide?

Blocks complex IV

153

What is the treatment for cyanide poisoning?

nitrates and ferric Fe (to cause cyanide to bind to Hb rather than cytochrome)

154

What is the purpose of adding carbs to proteins?

Increase solubility

155

What is mutorotation in terms of carbs?

Switching between the alpha and beta forms in free solution

156

in alpha glucose, is the C1 OH group on the same or opposite side as C6?

opposite C6

157

in beta glucose, is the C1 OH group on the same or opposite side as C6?

same side as C6

158

What are advanced glycosylation end products?

highly reactive glycosylated chemicals

159

Reduction of glucose leads to the formation of what two products?

Sorbitol and inostiol

160

What is the isoform of hexokinase in the liver called?

Glucokinase

161

What is the purpose of adding sulfur to carbs?

Needed for ECM production (adds a negative charge as well)

162

What does it mean to activate a sugar?

Transfer it to an nucleotide trisphosphate

163

What are the enzymes that form glycosidic bonds?

Glycosyltransferases

164

Maltose is a disacharride of what two molecules?

Glucose x2

165

lactose is a disacharride of what two molecules?

Galactose and glucose

166

Sucrose is a disacharride of what two molecules?

Glucose and fructose

167

Why is sucrose less reactive than other disacharides?

no free reducing end

168

Amylose and amylopectin are polymers of what molecule?

alpha-Glucose

169

Cellulose has what kind of glucose bonds?

Beta

170

What is the difference between amylopectin and glycogen?

More branching on glycogen

171

What is the function of GAGs in animals?

Structural support

172

What is the enzyme that breaks beings the breakdown of starch/glycogen in the saliva? What are the main products?

a-amylase

Maltose and maltotrioses

173

sucrose is degraded by what enzyme in the gut?

sucrase/isomaltase

174

What are the next two enzymes that break down the porducts of alpha amylase?

isomaltase and glucosidase

175

Where does SGLT 1 get its energy from?

Na/K transporter

176

Where is GLUT 1 found? What does it do?

Everywhere, basal glucose uptake

177

GLUT2 does what?

removes glucose from liver, intestine, gives to blood

178

What does GLUT3 do?

basal glucose uptake

179

what does GLUT 4 do?

INDUCIBLE BY INSULIN
muscle and adipose tissue gluc uptake

180

What does GLUT 5 do?

Uptake fructose in liver. NOT affected by insulin

181

What cells produce fructokinase?

Hepatocytes

182

What is the cause of fructosuria? Is this severe?

Defective fructokinase
Benign

183

What is the cause of heriditary fructose intolerance? Symptoms?

Aldolase B defect.

Accumulates fructose-1-phosphate in liver, phosphate pools drained

184

What are the three causes of galactosemia?

1. Defect galactokinase
2. Defect in galactose-1-phosphate uridyltransferase
3. Defect in UDP galactose epimerase

185

What are the three regulated enzymes in glycolysis?

Hexokinase
phosphofructokinase
pyruvate kinase

186

What stimulates/inhibits hexokinase

S: insulin
I: G6P, acetyl-coa,

187

What stimulates/inhibits PFK I?

S: ADP, AMP, F(2,6)bisphosphate
I: ATP, citrate

188

What stimulates/inhibits Pyruvate kinase?

S: fructose 1,6, bisphosphate, insulin
I: ATP

189

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

190

What is the essential enzyme in the Cori cycle?

Lactate dehydrogenase

191

What happens in pyruvate kinase deficiency?

Pyruvate--> lactate, lactic acidemia

192

How does arsenic exert its effects?

Takes the place of phosphate in rxn from G3P to 1,3 BPG.

193

Can FAs be used to generate glucose?

No

194

Where does the conversion of pyruvate to OAA occur?

mitochondria

195

Where does the conversion of OAA to PEP occur?

mito or cyto

196

What is the hormone that mothers produce that stimulates milk production?

Prolactin

197

Glucose-6-phosphate dehydro is regulated how?

Inhibited by NADPH

198

Deficiency of Glucose-6-phosphate dehydrogenase leads to what disease? What are they sensitive to?

G6PD deficiency = sensitivity to H2O2, fava beans, infection

199

What is glycogenin?

The substance that glycogen is synthesized on

200

Why don't muscles respond to glucagon?

They lack glucose-6-phosphatase

201

Does phosphorylation favor glycogen creation or degadation? (e.g is glycogen phosphorylase active in the phosphorylated state or not)

degradation

202

Phosphorylation of glycogen synthase does what (inactivates or activates it)?

INactivates it

203

Phosphorylation of glucose-6-phosphatase does what (inactivates or activates it)?

Activates it

204

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

205

What is van gierke's disease?

defect in glucose-6-phosphatase. leads to increased liver stores

206

What is Pompe's disease?

Defiecicncy in acid maltase (alpha-glucosidase) that is present in lysosomes. Lysomal glycogen accumulates

207

What is cori disease?

Defect in the glycogen debranching enzyme

208

What is McArdles disease?

defect in glycogen phosphorylase, muscles cannot use glycogen

209

What are the two pathways that alcohol is metabolized?

Via p450 or by two enzymes (alcohol dehydo, + aldehyde dehydro)

210

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

211

Where does protein glycosylation (the process of it) take place?

Golgi and ER

212

What are the two Amino acids that are used to attach carbs to?

S and N

213

accharide chain.
The monomeric units for the synthesis of glycosaminoglycans
are what?

activated sugar molecules

214

What is the enzyme that adds sulfur groups to GAGs?

sulfotransferases

215

Proteoglycans are degraded in what?

Lysosomes

216

What is the defective enzymes in hunter syndrome? What accumulates?

Iduronate sulfatase deficiency causes dermatan and heparan sulfate to accumulate

217

What is the defective enzymes in Hurler syndrome? What accumulates?

Alpha-Iduronate sulfatase deficiency causes dermatan and heparan sulfate to accumulate

218

What reaction does the enzyme UGT catalyze?

Addition of UDP glucose to xenobiotics

219

Up to what carbon number can the body synthesize unsaturated FAs?

9

220

What are the two essential FAs?

Linoleic and Linolenic acid

221

What are the three enzymes involved in carnitine transport?

Acyl-CoA
CPT I
CPT II

222

Defects in Carnitine transport (primary carnitine deficiency) leads to what physiological state?

Fasting hypoglycemia

223

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)?

Enoyl-CoA isomerase

224

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?

Reductase
Enoyl-Coa isomerase

225

Where does beta-oxidation occur in the cell?

Mitochondria, some in peroxisomes

226

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

227

What is actue fatty liver of pregnancy?

Deficiency of LCFA dehydrogenase

228

Acyl-Coa dehydrogenase deficiencies present as what?

Non-ketotic fasting hypoglycemia

229

What is Refsum disease?

problem with digesting phytanic acid (metabolite of chlorophyll). Results in neurological defects

230

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

231

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?

Acetoacetate:succinyl-CoA transferase

232

For every turn of the FA synthesis cycle, how many NADPHs are used?

2

233

Where does the elongation of FAs occur?

Mito or ER

234

How does elongation of FAs occur in the the ER?

Similar to FA synthase

235

How does elongation of FAs occur in the mito?

reverse beta oxidation

236

True or false: lipid droplets are stored surrounded by a lipid bilayer, which has perilipin and lipases in it

False--monolayer. O/w true

237

What is the glyoclytic intermediate for glycerol?

DHAP

238

What is the enzymes that converts DHAP to glycerol or v.v.?

Glycerol phosphate dehydrogenase (note, glycerol, not glyceraldehyde)

239

What are the two enzymes involved in the synthesis of TAGs? What is the substrate they act on?

Acyltransferases
Phosphatidate phosphatase

Glycerol 3 phosphate

240

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

241

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)

242

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)

243

How does malonyl CoA inhibit FA degradation?

Inhibits CPT I

244

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

245

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

246

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?

Phosphocholine cytidyltransferse

DAG is transferred to the activated CDP-choline via choline phosphotransferase

247

What is the enzyme that synthesizes phosphatidyl serine from phosphatidyl ethanolamine?

Phosphatidylserine synthase

248

What is the enzyme that synthesizes phosphatidyl choline from phosphatidyl ethanolamine?

Phosphatidylethanolamine N methyltransferase

249

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

250

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

251

What is the enzyme that catalyzes the synthesis of phosphatidyl inositol from inositol and an activaed DAG?

Phosphatidyl inositol synthase

252

What is cardiolipin? What role does it play?

Two DAGs attached to one another via a methyl linkage

Helps with folding of mito ETC

253

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

254

Why are phospholipases important?

Allow for modification of newly synthesized lipids

255

What is the enzyme that synthesizes PGG from arachiodonic acid?

COX1/2

256

What is the enzyme that takes PGG produced from COX1/2 and turns it into PGH?

PGH synthase

257

What is the enzyme that synthesizes thromboxane? What is the precursor?

Precursor =PGH

Thromboxane synthase

258

What is the enzyme that starts arachidonic acid down the pathway of leukotriene synthesis?

Lipoxygenase

259

What is the target for asthma drugs that stops the production of leukotrienes?

Lipoxygenase inhibitors

260

Where does the synthesis of plasmalogens take place?

Peroxisomes

261

What are the amino acid and FA used to synthesize ceramide, the precursor for sphingolipids?

Serine + Palmitoyl-CoA

262

The transfer of phosphocholine to ceramide yields what?

Shingomyelin

263

The transfer of glucose/galactose to ceramide yields what?

Cerebrosides

264

The transfer of suflate to cerbrosides yields what?

Sulfatide

265

The transfer of 2-4 neutral sugars to ceramide yields what?

Globosides

266

The transfer of NANA to ceramide yields what?

Gangliosides

267

What is the enzyme defect in Gaucher's disease, and what accumulates?

Beta-glucosidase, accumulates glucocerebroside. Leads to hepatosplenopmegaly

268

Where is the cell does cholesterol synthesis occur?

Cytosol

269

What can Farnesyl be used for, besides cholesterol synthesis?

Dolichol phosphate
prenylation of proteins
element of CoQ

270

Two farnesyls combine to form what? What comes from this?

Squalene
Lanosterol

271

What are the three ways in which HMG reductase is regulated?

AMPDK inactivates

Insulin dephos it

Cholesterol inhibits it

272

What is the target of Statins?

HMG reductase

273

What is the enzyme that esterifies cholesterol?

LCAT

274

What enzymes breaks down cholesterol?

Humans lack this enzyme

275

How do insulin, cortisol, and glucagon affect HSL?

Insulin inhibits it
Glucagon stimulates it
Cortisol induces it

276

What are the four apoproteins?

Apoprotein A, B, C, and E

277

What is the function of apoprotein A?

Have LCAT, and will extract lipids from cells

278

What is the function of apoprotein B?

Structural and receptor

279

What is the function of apoprotein C?

Modulate function of lipoprotein lipase

Liberate fatty acids and release them to cells

280

What is the function of apoprotein E?

Receptor ligand

281

Apoprotein B48 is found where?

On chylomicrons

282

What are the two reasons for hyperlipidemia observed in pts with DM?

Overactive hormone sensitive lipase
Inactive lipoprotein lipases (part of LDL)

283

What is the defective/deficient enzyme in Tyrosinemia I?

Tyrosine amino transferase

284

What is the defective/deficient enzyme in Tyrosinemia II?

Maleylacetoacetate hydrolase

285

What is the defective/deficient enzyme in alkaptonuria?

homogentisate oxidase

286

What is the defective/deficient enzyme in homocysteine uria?

Cystathionine Beta-synthase

287

Why must [K] be monitored closely in DM II pts?

Because K is lost in polyuria, and is taken in with insulin administration

288

What are the three major consequences of uncontrolled DM?

Neuropathy
Nephropathy
Retinal damage

289

What is the signal for the release of insulin?

ATP, causes the release of Ca

290

What are the two important enzymes the insulin increses the transcription of?

Acetyl-CoA carboxylase
FA synthase

291

What is the one important enzyme that insulin decreases the transcription of?

PEP carboxykinase

292

Why does EtOH exacerbate porphyrias?

Increases heme synthesis for the p450 enzymes

293

WHat is AIP (acute intermittent porphyria?)

Defeciency in porphobilinogen deaminase

294

What is the cause of prophyria cutanea tarda?

Deficiency of uroporphyrinogen, leads to build up of UPG III

295

What part of the heme synthesis pathway does Pb inhibit?

ferrochelatase and PBG synthase

296

What is the difference between direct and indirect bili?

Direct = water soluble
Indirect = not so much

297

What type of bili is excreted in the urine? In the feces?

Urobiliogen in the feces
Urobilin in the urine

298

What are the the causes of prehepatic jaundice?

Hemolytic diseases

299

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)

300

What are the two inhibitors of PRPP synthetase?

ADP and GDP

301

What are the two inhibitors of amidoribosyltransferase?

AMP and GMP

302

What is hyperuricemia?

Excess uric acid in the blood due to reduced excretion or increased production of uric acid

303

HOw does EtOH consumption increase the effects or uric acid?

decreased excertion of uric acid, and increased production

304

What is the action of allopurinol?

Decrease the production of uric acid, by inhibiting xanthine oxidase

305

What is orotic acid uria?

Defect in UMP synthease (leads to megaloblastic anemia)

306

What is the enzyme that catalyzes CTP from UTP?

CTP synthase

307

What is the enzyme that regulates pyrimidine synthesis?

Carbamoyl phosphate synthase II

308

Where are the inhibitors/activators of carbamoyl phosphate synthetase?

Inhibited by UTP and activated by PRPP

309

What is the enzyme that catalyzes the production of dNDPs from NDP

Ribonucleotide reductase

310

What is the chemical that is reduced i the ribonucleotide ruductase reaction? What is the electron donor that regenerates this?

Thioredoxin
NADPH (via thioredoxin reductase)

311

SCID can be caused by a deficiency of what?

Adenosine deaminase

312

What is the effect of hydroxyurea on ribonucleotide reductase?

inhibits it

313

What is the enzyme that converts dUMP to dTMP? What other substrate is needed for this reaction?

Thymidylate synthase
N5N10 methylne THF (goes to dihydrofolate)

314

What is the action of 5-flurouracil?

COonverted to FUMP, and inhibits thymidlyate synthatse

315

Degradation of pyrimidine nucleotides yields what?

beta-alanine, except for dTMP

316

Degradation of dTMP laeds to what?

Beta-aminobutryate

317

What are the two enzymes the are needed for purine salavege?

HGPRTase (forganin and hypoxanthine)

APRTase for Adendine

318

How are HGPRTase and APRTase regulated?

product inhibition

319

How do the salvage pathways inhibit de novo syntehsis?

Take up PRPP and incrased AMP/GMP withich inhibit amidophosphpribosltrasferase

320

What is the only purine nucleoside that can be taken up by humans directly?

Adenosine

321

What is the cause of Lesc-Nyhan syndrome?

Deficiency of HGPRTase--leads to MR

322

What is the enzyme that allows for the uptake or pyrimidine uptake? What pyrimidine cannot be taken up?

Pyrimidine phosphoribosyltransferase

Cytosine

323

What is the two ways in which cytochrome p450 induces liver damage?

NADPH oxidation
Generation of a hydroxyethyl radical

324

Whatr is the function of superoxide dismutase?

Takes 2O2- and reduces it to hydrogen peroxide

325

What is the function of catalase?

Detoxifies hydrogen peroxide by converting it into water

326

What is the function of Glutathinoe peroxidase?

takes hydrogen peroxide and reduces it to water

327

What are the three vitamins that play a role in antioxidation?

Vit A, C, E

328

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

329

What is the ultimate source electrons for the reduction of radicals?

NADPH

330

What is the function of methhb?

Repairs Fe 3+ to Fe2+, whose oxidation is the result of hydrogen peroxide

331

What is the only way that malondialdehyde is produced?

From the hydroxy radical reaction of PUFAs

332

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

333

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

334

What does most of the satillite DNA acount for?

centromeres and telomeres

335

What are pseudogenes?

Duplicated genes that have been inactivated

336

Palindromic sequences of DNA nucleotides create what type of structure/.

Cruciform

337

Long runs of pryimidine/purine nucleotides create what type of structure?

Triple helix

338

What is the target of naldixic acid and cipro?

Target prokaryotic topoisomerase II

339

Incorrect recombination where unequal corssover occurs is more likely to happen where on the chromosomes (think base pairs)?

Where there are large, repetitive sequences

340

Where do strand slippages occur?

Sequences of repeats, such that the DNA can loop back on itself

341

What are chiasmata?

Sites of chromosomal crossover

342

What is a genome mutation?

Change in the number of chromosomes

343

HNPCC (lynch syndrome) is the result of what?

Mutations in the DNA mismatch repair mechanism

344

What is the role of DNA glycosylases?

Recognize specific DNA mismatches and remove them

345

When is DNA base excision repair used? Nucleotide excision repair?

Base is just for point mutations
Nucleotide is when there are thymine dimers

346

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

347

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

348

What is the cause of xeroderma pigmentosum?

Defect in nucleotide excision repair

349

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

350

What is cyclophosphamide what what does it do?

Cyclic drug that turns into phosphoramide mustard and cuases DNA strand links

351

What does SP1 (the general promoter protein) bind to?

GC rich regions box

352

What does the general promotor protein NF1 bind to?

CAAT box

353

What is the effect of the death cap mushroom?

Inhibits Pol II. Liver failure

354

What is the action of Rifampicin?

Inhibits RNA polymerase II in TB

355

What is the base that begins the process of splicing?

Adenine residue

356

What is the polyadenylation signal?

DNA sequence that direct the application of a 3' tail

357

What is the genetic problem in beta thalessemia?

mutation in the Beta-globin gene splice site

358

What is the genetic basis for PKU?

mutation in the 5' splice site

359

SRE1 is a transcription binding protein for what pathway?

LDL

360

What does the protein CRSP do?

binds to SP-1 in the LDL transcription complex

361

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.

362

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.

363

What are the two proteins whose transcription is induced by cort binding to the cortisol receptor?

PEP carboxykinase
Lipoprotein lipase

364

What is bound to the thyroid receptor in the nucleus?

RXR

365

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

366

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.

367

What is the action of tamoxifen?

Competitive inhibitor of the estrogen receptor

368

What is ataxia teleangiectasia?

Inhibition of of ATM, leading to easily developing lymphomas and leukemias

369

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

370

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

371

Ras mutations are particularly prominent in what type of cancers?

Pancreatic

372

What is Burkett's lymphoma?

Due to the translocation of a c-myc gene from chromosome 8 to 14. B cells become cancerous

373

Retinoblastoma is the result of what?

Mutation in RB1 gene. Follows two hit model

374

What is the protine that associates with p53 and causes its instability?

Mdm2

375

Why is it significant that p53 functions as a homotetramer?

One change leads to dysfunctions protein

376

What is Li-Fraumieni syndrome?

mutation in p53, leading to a crap ton of cancers

377

What is the function of neurofibromin?

Accelerates that degradation of neurofibromin

378

What are the two proteins that are involved in HPV? What do they inhibit?

E6 inhibits p53
E7 inhibits Rb

379

What do the BRCA1/2 genes do?

Involved in DNA double stranded repair and getting proteins to the sites of repair

380

What is the protein that is involved in angiogenesis of tumor cells?

HIF-1alpha-beta

381

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

382

What are the proteins that usually hold epithelial cells together?

E-cadherin

383

What are the enzymes that tumor cell overexpress and lead to intravasation?

Matrix metalloproteases (MMPs)

384

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

385

What pathway is the APC gene involved in (in FAP)?

WNT pathway

386

What is the protein in the WNT pathway that actually stimulates transcription?

Beta-Catenin

387

What does Beta-catenin stimulate specifically?

Nyc and Cyclin D

388

How does the APC protein regular the beta-catenin protein?

Forms a destruction complex normally, unless a signal is received.

389

What are the genes that are mutated in HNPCC? What do each of these do?

MSH2 - identifies DNA mismatches
MLH1 - repairs DNA mismatches

390

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

391

What is the function of imatinib mesylate (Gleevec)?

Inhibits the Y-kinase of Bcr/Abl1 mutation of the Philadelphia chromoesome of chronic myeloid leukemia

392

What is the function of herceptin (Trastuzumab)?

Inhibits the HER2/Neu receptor

393

LHON is caused by a mutation in what gene?

ND1