Final Review Flashcards
(393 cards)
1
Q
Oxidoreducatase catalyze what reactions?
A
Redox
2
Q
What class of enzymes are oxidases?
A
Oxidoreductases
3
Q
What class of enzymes are oxygenases?
A
Oxidoreductases
4
Q
What class of enzymes are reductases?
A
Oxidoreductases
5
Q
What class of enzymes are dehydrogenases?
A
Oxidoreductases
6
Q
What class of enzymes are kinases?
A
Transferase
7
Q
What class of enzymes are carboxylases?
A
Transferase and ligases
8
Q
What class of enzymes are glucokinase
A
Transferase
9
Q
What class of enzymes are glucosidases?
A
Hydrolase
10
Q
What class of enzymes are ATPases?
A
Hydrolase
11
Q
What class of enzymes are phosphatases?
A
Hydrolase
12
Q
What class of enzymes are peptidases?
A
Hydrolase
13
Q
What class of enzymes are lipases?
A
Hydrolase
14
Q
What class of enzymes are lyases?
A
Lyases
15
Q
What class of enzymes are mutates?
A
isomerases
16
Q
What class of enzymes are epimerases?
A
isomerases
17
Q
What class of enzymes are racemaces?
A
isomerases
18
Q
What class of enzymes are synthases?
A
ligase
19
Q
What class of enzymes are synthetases?
A
ligase
20
Q
What are hydrolases?
A
cleave bonds by adding water
21
Q
What are lyases?
A
Break bonds (usually C-C)
22
Q
isomerases ligases?
A
form bonds (need energy input)
23
Q
What are metalloenzymes?
A
Enzymes that contain metal
24
Q
What are prosthetic groups?
A
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
