Biochemistry Flashcards
1
Q
Metalloproteinase
A
breakdown collagen for remodeling (ie destabilize arterial plaques)
2
Q
Prolyl hydroxylase
A
hydroxylation of proline on pro collagen to form a stable collagen triple helix (stabilizes collagen)
3
Q
Lysyl oxidase
A
strengthens collagen fibers by converting lysine to aldehyde (stabilizes collagen)
4
Q
Procollagen peptidase
A
cleaves the terminal ends of pro collagen molecules to form insoluble tropocollagen that will aggregate to form collagen fibrils
5
Q
Ehlers-Danlos pts have a deficiency of what enzyme
A
Procollagen peptidase –> disorganized collagen bundles
6
Q
Tetrahydrobiopterin
A
cofactor in the synthesis of DA, 5-HT, & Tyrosine (DA & melanin precursor)
7
Q
Nucleosome
A
core of histones (H2A, H2B, H3, H4) + DNA
8
Q
Histones are composed of what a.a.?
A
Arginine & lysine === positive-charge
9
Q
DNA is negatively charges d/t
A
phosphates
10
Q
Linker histone
A
H1
11
Q
Deamination of cytosine
A
uracil
12
Q
Which nucleotides raise the melting temp of DNA?
A
Cytosine & Guanine rich DNA (3H bonds)
13
Q
Which a.a. are necessary to make purines?
A
glycine, glutamine, & aspartate
14
Q
What 5 substances are needed to make a purine?
A
glycine, glutamine, & aspartate + tetrahydrofolate & CO2
15
Q
Which a.a. are necessary to make pyrimidines?
A
aspartate & glutamine
16
Q
What 4 substances are needed to make a pyrimidines?
A
aspartate, CO2, glutamine, ATP
17
Q
Carbamoyl phosphate
A
necessary for pyrimidine synthesis, composed from CO2, glutamine, & ATP
18
Q
Rate-limiting step for pyrimidine synthesis
A
Carbamoyl phosphate synthetase-2 (CPS-2)
19
Q
CPS-2
A
Pyrimidine synthesis, found in cytosol, Nitrogen source is Glutamine
20
Q
CPS-1
A
Urea cycle, found in mitochondria, Nitrogen source is Ammonia
21
Q
CPS-2 catalyzes
A
CO2+ glutamine + ATP –> Carbamoyl phosphate
22
Q
Orotic aciduria disease: deficiency in
A
UMP synthase
23
Q
Ribonucleotide reductase catalyzes
A
UDP –> dUDP (pyridine synthesis)
24
Q
What drug inhibits Ribonucleotide reductase?
A
Hydroxyurea
25
Hydroxyurea is used to treat
Sickle Cell
| Chemotherapeutic (CML, melanoma)
26
Thymidylate synthase catalyzes
dUMP --> dTMP (pyridine synthesis)
| Tetrahydrofolate is used in this step
27
Dihydrofolate reductase catalyzes
dihydrofolate ---> tetrahydrofolate for the conversion of dUMP -> dTMP
28
Which drug inhibits Thymidylate synthase?
5-Flourouracil (uracil analog)
29
5-Flourouracil is used to treat?
Chemotherapeutic agent (adenocarcinoma, colon)
30
Which drug inhibits Dihydrofolate reductase?
Methotrexate & Trimethoprim (prokaryotes)
31
Orotic aciduria
AR disease that causes orotic aciduria + megaloblastic anemia (cannot synthesize pyrimidines)
32
Ornithine Transcarbamylase Deficiency
orotic aciduria + hyperammonemia
33
Tx of orotic aciduria?
Uridine supplement
34
Rate-limiting step of Puridine synthesis?
Glutamine PRPP Amidotransferase (PRPP -> IMP)
35
Which drug inhibits Glutamine PRPP Amidotransferase?
6-Mercaptopurine, Azathioprine (6-MP analog)
36
IMP dehydrogenase catalyzes
IMP ---> GMP
37
Which drug inhibits IMP dehydrogenase?
Mycophenolate
38
Xanthine Oxidase catalyzes
Hypoxanthine --> xanthine
| xanthine --> uric acid (purine degradation)
39
Which drug inhibits Xanthine oxidase?
Allopurinol
40
Allopurinol will increase the serum concentration of which drugs?
6-Mercaptopurine & Azathioprine
41
HGPRT catalyzes
Guanine &/or Hypoxanthine --> GMP &/or IMP (Purine salvage)
42
Lesch-Nyhan Syndrome - deficiency of
HGPRT enzyme (inability to salvage purines)
43
Lesch-Nyhan Syndrome Sx
gout, aggressive behavior, low IQ, self-mutilation (lip biting), movement disorder
44
Tx for Lesch-Nyhan Syndrome
Tx gout w/ Allopurinol or Febuxostate
45
Genetics of Lesch-Nyhan Syndrome
X-linked
46
SCID is most frequently caused by a deficiency in
Adenosine Deaminase
47
Adenosine deaminase catalyzes
adenosine --> inosine (purine degradation)
48
Rate-limiting step in purine synthesis?
Glutamine PRPP Amidotransferase
49
Rate-limiting step in pyrimidine synthesis?
CPS-2
50
The carbon source in purine synthesis comes from?
CO2, Glycine, Tetrahydrofolate
51
The carbon source in pyrimidine synthesis comes from?
Aspartate, CO2
52
Hydroxyurea
ribonucleotide reductase inhibitor
53
Methotrexate & Trimethoprim
Dihydrofolate reductase inhibitor
54
5-FU
Thymidylate synthase inhibitor
55
Mycophenolate
IMP dehydrogenase inhibitor
56
6-MP
PRPP amidotransferase inhibitor
57
Boy w/ self-mutilating behavior, low IQ, & gout
Lesch-Nyhan Syndrome (HGPRT def)
58
Orotic aciduria + hyperammonemia
Ornithine Transcarbamylase Deficiency
59
Orotic aciduria + normal serum ammonia
Orotic aciduria
60
Megaloblastic anemia that does not improve w/ folate or B12
Orotic aciduria
61
DNA Helicase
unwinds DNA during DNA replication
62
Topoisomerase
nicks DNA downstream to reduce the negative supercoils during DNA replication
63
Single Stranded Binding Proteins
Binds the the unwound DNA strands to stabilize the single strands
64
Which ABX class inhibits Topoisomerase?
Fluoroquinolones
65
Which chemotherapeutic agent inhibits Topoisomerase?
Etoposide
66
Etoposide is used to Tx?
solid tumors (Small cell lung carcinoma)
67
Auto-antibody that binds Topoisomerase?
Anti-Scl-70
68
Anti-Scl-70 is assoc w/
Diffuse Scleroderma
69
Primase
adds ribonucleotides to allow DNA pol III to bind
70
DNA polymerase III
binds double-stranded DNA and synthesizes in 5'->3' direction (prokaryotes: both leading & lagging strand)
71
Primosome
DNA helicase + Primase complex
72
DNA polymerase I
removes ribonucleotides from RNA primer segment and replaces them w/ deoxyribonucleotides
73
DNA ligase
joints Okazaki fragments on lagging strand
74
Eukaryotic DNA pol alpha
synthesizes the lagging strand & synthesizes RNA primer
75
Eukaryotic DNA pol delta
synthesizes the leading strand
76
Eukaryotic DNA pol beta
DNA repair (Base-excision repair)
77
Eukaryotic DNA pol gamma
mitochondrial DNA replication
78
Silent mutation
single base mutation, often in the 3rd base --> same amino acid is coded
79
Missense mutation
single base mutation --> codes for a different amino acid
80
Nonsense mutation
single base mutation --> STOP codon
81
Frameshift mutation
addition/deletion mutation --> shifts reading frame
82
UV damage to DNA causes
pyrimidine dimer (thymidine cross-links on SAME DNA strand)
83
Mismatch repair
removes bases (including mismatched base) & replaces bases
84
Nucleotide excision repair
repair bulky DNA damage (UV damage)
85
Enzymes utilized in Nucleotide excision repair
endonuclease (removal/excision), DNA pol beta (insertion), DNA ligase (seals)
86
Base Excision Repair
removes just damaged base (small)
87
Enzymes utilized in Base excision repair
Glycosylase (removes damaged base)
Endonuclease (excises DNA backbone)
DNA pol beta & DNA ligase (insert/seal)
88
Non-Homologous End Joining
joins end of dsDNA break
89
Hereditary Nonpolyposis Colorectal Cancer - defective
mismatch repair
90
Xeroderma Pigmentosum - defective
nucleotide excision repair (UV light DNA damage)
91
Bloom Syndrome - mutation in
DNA helicase -> impaired DNA replication & repair
92
Ataxia Telangiectasia - defective
repair of dsDNA breaks (ionizing radiation DNA damage)
93
BRCA-1/-2 - defective
dsDNA break repair
94
Start codon
AUG -> Methionine
95
Stop codon
UGA, UAA, UAG
96
Which RNAs are synthesized in the nucleoplasm?
mRNA, tRNA
97
Which RNAs are synthesized in the nucleolus?
rRNA
98
Operon
transcribed gene + promoter + regulatory regions
99
Transcription factor
bind promoter regions (on/off)
100
What are the 3 main promoter regions?
-75 CCAAT box, -25 TATA box, -10 TATAAT box
101
Operator region
binds repressor or inducer, located b/w promoter and start site (on/off)
102
Response elements
enhancer or repressor region that increase or decrease the rate of transcription (rate control) may be located any distance from gene
103
Helix-loop-helix
allows protein to interact
104
Helix-turn-helix
allows protein to interact
105
Zinc finger
Zinc atom that incorporates into DNA
106
Leucine zipper protein
Many leucine residues, structural motif
107
What 2 conditions must be met for the lac operon to be turned on?
excess lactose + NO glucose
108
Lac operon activation causes transcription of
b-galactosidase
109
How does the absence of glucose contribute to turning on the lac operon?
when there is no glucose --> CAP (TF) binds the promoter region
110
How does excess lactose contribute to turning on the lac operon?
excess lactose --> lac repressor is released from the operator
111
Eukaryotic RNA pol 1
synthesizes rRNA
112
Eukaryotic RNA pol 2
synthesizes mRNA
113
Eukaryotic RNA pol 3
synthesizes tRNA
114
alpha-amanitin (mushroom toxin) inhibits
Eukaryotic RNA pol 2 leading to hepatotoxicity
115
Prokaryotic RNA pol
RNA pol 1 only
116
Which ABX inhibits RNA pol?
Rifampin
117
Hairpin Loop
termination of prokaryotic RNA transcription:
GC-rich regions of ssRNA binds forming a hairpin loop
Uracil rich region follows w/ weak bonds -> breaks off & RNA pol dissociates
118
Rho factor
RNA-dependent ATPase that knocks RNA pol off for termination of prokaryotic RNA transcription
119
S-adenosyl-methionine
attaches 7-methyl-guanosine cap to 5' end of hnRNA
120
Poly-A-Polymerase
Adds adenines to 3'end of hnRNA
121
Spliceosome
splice out introns of hnRNA
122
mRNA processing requires
Addition of 5' 7-methyl-guanosine cap
3' Poly-adenosine tail
Splicing of introns
123
Aminoacyl tRNA synthase
matches amino acids to tRNA
124
Aminoacyl tRNA synthase always adds amino acids to
the 3' end of the tRNA
125
Eukaryotic rRNA subunits
40S & 60S --> 80S
126
Prokaryotic rRNA subunits
30S & 50S --> 70S
127
50S subunit contains
23S ribosomal RNA
128
Initiation of translation
Initiation factor-2 (IF-1, IF-2, IF-3) binds 30S, then tRNA-Met, then binds 50S by hydrolyzing GTP
129
A site of the ribosome
binds all incoming aminoacyl tRNAs (except the 1st Met-tRNA)
130
P site of the ribosome
site of growing polypeptide chain (site where 1st Met-tRNA binds)
131
E site of the ribosome
exit site of free tRNA
132
Elongation factors
assist aminoacyl-tRNA binding to A site
133
Peptidyltransferase
w/in 23S rRNA
| catalyzes the transfer of peptide chain from the P site to the a.a.-tRNA in the A site
134
Translocation
occurs during elongation, transfer tRNA form A to P site & slides the ribosome down to the next codon
135
Elongation factor-G
catalyzes translocation in prokaryotes
136
Elongation factor-2
catalyzes translocation in eukaryotes
137
What bacterial toxins inhibit EF-2?
Diptheria toxin & Exotoxin A
138
Termination
Release Factor causes dissociation of the polypeptide from the ribosome
139
Peptide modifications leading to functional protein
trimming, glycosylation, hydroxylation, phosphorylation
140
Which ABX binds the 30S subunit to prevent association w/ the 50S subunit?
Aminoglycosides
141
Which ABX bind 30S subunit to inhibit aminoacyl-tRNA from binding the A site?
Tetracyclines
142
Which ABX bind 50S subunit to inhibit peptidyltransferase?
Chloramphenicol
143
Which ABX bind 50S subunit to inhibit association w/ 30S?
Linezolid
144
Which ABX bind 50S subunit to inhibit translocation?
Macrolides, Clindamycin, Lindomycin, Streptogramin
145
AD pedigrees
M & F are affected, 50% of offspring, every generation
146
AR pedigrees
Non-successive generations, 25% of offspring
147
X-linked Recessive pedigrees
Typically only Males affected; females 50% of carrier, males of offspring 50% affected
148
X-linked Dominant pedigrees
all daughters of affected males will be affected
149
Mitochondrial Inheritance pedigrees
all offspring of affected mom will be affected
150
Anticipation
age of onset is earlier or more severe w/ successive generations
151
What disease is an example of anticipation?
Huntington Disease
152
Incomplete Penetrance
how often a mutant genotype causes a mutant phenotype
153
Pleiotrophy
1 gene causes many different effects (PKU)
154
Locus Heterogeneity
multiple mutations could cause the same phenotype (Marfans)
155
Codominance
both alleles are equally expressed (ABO type)
156
Variable expression
severity of phenotype varies in individuals (tuberous sclerosis)
157
Imprinting
phenotype differences depend on whether mutation came from mom or dad (angel man & prader-willi)
158
Prader-Willi Syndrome
maternal imprinting + paternal deletion on chromosome 15
159
Angelman Syndrome
paternal imprinting + maternal deletion on chromosome 15
160
Hardy-Weinberg Eq
p+q = 1
| p^2 + 2pq + q^2 = 1
161
Northern blot
gel electrophoresis RNA samples + DNA probe
162
Southern blot
gel electrophoresis DNA samples + DNA probe
163
Western blot
gel electrophoresis protein samples + Antibody probe
164
Southwestern blot
DNA binding proteins
165
Direct ELISA
antibody in well + sample (Ag)
| Does pt have X antigen?
166
Indirect ELISA
antigen in well + sample (Ab)
| Does pt have X antibody?
167
Screening test for HIV?
Indirect ELISA
168
Confirmatory test for HIV?
Western blot
169
Kayotyping
Dx chromosomal imbalance
170
GLUT-1
found on RBCs & BBB
| mediates basal glucose uptake
171
GLUT-2
found on hepatocytes & pancreatic b-cells
172
GLUT-3
found on neurons & placenta
173
GLUT-4
found on skeletal mm. & adipose tissue
| insulin-dependent glucose uptake
174
GLUT-5
Fructose uptake (esp in GIT)
175
Hexokinase catalyzes
glucose --> glucose-6-phosphate (traps glucose in cell)
176
Glucokinase catalyzes
glucose --> glucose-6-phosphate (traps glucose in cell)
| found in liver & pancreatic b-cells
177
Hexokinase kinetics
low Km, higher glucose affinity, low Vmax, not induced by insulin
178
Glucokinase kinetics
High Km, high Vmax, induced by insulin
179
Rate-limiting step of glycolysis
Phosphofructokinase-1
180
What substances activate Phosphofructokinase-1?
AMP, Fructose-2,6-bisphosphate
181
What substances inhibit Phosphofructokinase-1?
ATP, Citrate
182
Pyruvate kinase catalyzes
Phosphoenolpyruvate --> Pyruvate
183
What substances activate Pyruvate kinase?
Fructose-1,6-bisphosphate
184
What substances inhibit Pyruvate kinase?
ATP & Alanine
185
Major Sx of Glycolytic enzyme deficiency?
Hemolytic anemia
186
Most common Glycolytic enzyme deficiency?
Pyruvate Kinase deficiency
187
High glycogen, elevated fructose-6-phosphate & low pyruvate?
Phosphofructokinase-1 deficiency
188
How does insulin enhance glycolysis?
insulin --> activate PFK-2 --> high Fructose-2,6-bisphosphate (stimulates PFK-1)
189
How does glucagon enhance gluconeogenesis?
glucagon --> activate FBPase-2 --> high Fructose-6-phosphate (for gluconeogenesis)
190
PFK-2 catalyzes
Fructose-6-phosphate ---> Fructose-2,6-bisphosphate
191
FBPase-2 catalyzes
Fructose-2,6-bisphosphate --> Fructose-6-phosphate
192
Rate-limiting step of gluconeogenesis
Fructose-1,6-bisphosphatase
193
Pyruvate carboxylase catalyzes
pyruvate --> oxaloacetate
194
Pyruvate carboxylase requires what coenzyme
Biotin
195
What substance stimulates Pyruvate carboxylase?
Acetyl-CoA
196
PEP carboxylase catalyzes
oxaloacetate --> PEP
197
Fructose-1,6-bisphosphatase catalyzes
Fructose-1,6-bisphosphate --> Fructose-6-phosphate
198
What substances activates Fructose-1,6-bisphosphatase?
ATP
199
What substances inhibit Fructose-1,6-bisphosphatase?
AMP & Fructose-2,6-Bisphosphate
200
Glucose-6-phosphatase catalyzes
Glucose-6-phosphate --> Glucose (untraps glucose from cell)
201
Rate-limiting enzyme of de novo pyrimidine synthesis?
CPS-2
202
Rate-limiting enzyme of de novo purine synthesis?
Glutamine PRPP amidotransferase
203
Rate-limiting enzyme of glycogen synthesis
glycogen synthase
204
Rate-limiting enzyme of glycogenolysis
glycogen phosphorylase
205
Rate-limiting enzyme of TCA cycle?
isocitrate dehydrogenase
206
Rate-limiting enzyme of hexose monophosphate shunt?
glucose-6-phosphate dehydrogenase
207
UDP-glucose pyrophosphorylase catalyzes
Glucose-1-phosphate --> UDP-glucose
208
Glycogen synthase catalyzes
UDP-glucose --> alpha-1,4-glycosidic linkages
209
Branching enzyme catalyzes
UDP-glucose --> alpha-1,6-glycosidic linkages
210
Glycogen phosphorylase catalyzes
alpha-1,4-glycosidic linkages --> Glucose-1-phosphate
211
Phosphoglucomutase catalyzes
Glucose-1-phosphate --> Glucose-6-phosphate
212
Glucose-6-phosphatase catalyzes
Glucose-6-phosphate --> Glucose
213
alpha-1,6-glucosidase catalyzes
alpha-1,6-glycosidic linkages --> Glucose
214
McArdle Disease - deficient
Glycogen phosphorylase
215
McArdle Disease Sx
glycogen build-up in mm. -> rhabdomyolysis -> myoglobinemia -> renal failure
mm. cramping
216
Von Gierke Disease - deficient
glucose-6-phosphatase
217
Von Gierke Disease Sx
severe hypoglycemia, hepatomegaly (glycogen in liver), B/L enlarged kidneys, high serum lactate, uric acid & triglycerides
218
Von Gierke Disease Tx
frequent feedings + corn starch at night
219
Cori Disease - deficient
alpha-1,6-glucosidase
220
Cori Disease Sx
mild hypoglycemia, hepatomegaly, hyperlipidemia; normal lactate & uric acid
221
Pompe Disease - deficient
alpha-1,4-glucosidase in lysosomes
222
Pompe Disease - infantile form Sx
severe mm. weakness, cardiomegaly & heart failure, shortened life expectancy
223
Pompe Disease - adult form Sx
gradual mm. weakness, diaphragm weakness, & respiratory failure; no cardiac involvement
224
Pyruvate dehydrogenase catalyzes
Pyruvate ---> Acetyl-CoA
225
Pyruvate dehydrogenase cofactors
Thiamine pyrophosphate (B1) + Lipoic acid + Coenzyme A (B5), FAD (B2) + NAD+ (B3)
226
Rate-limiting step of the TCA cycle
Isocitrate dehydrogenase
227
Isocitrate dehydrogenase catalyzes
Isocitrate --> alpha-ketoglutarate
228
Citrate Synthase catalyzes
Oxaloacetate + Acetyl-CoA --> citrate
229
Alpha-ketoglutarate dehydrogenase catalyzes
alpha-ketoglutarate --> succinyl CoA
230
What 4 end products can be made from pyruvate?
Oxaloacetate, Alanine, Acetyl-CoA, Lactate
231
Which TCA cycle enzymes requires the same cofactors as pyruvate dehydrogenase?
Alpha-ketoglutarate dehydrogenase
232
Arsenic can inhibit
Lipoic Acid
233
Sx of arsenic exposure
diarrhea, vomiting, & GARLIC breath
234
Complex I of the ETC
NADH reductase
235
Complex II of the ETC
Succinate dehydrogenase + coenzyme Q
236
Complex III of the ETC
cytochrome b + c1
237
Complex IV of the ETC
cytochrome a + a3
238
ATPase of the ETC
high [H+] in the inter membrane space is utilized by the ATPase to make ATP
239
Uncoupling agents include
high-dose aspirin, 2,4-dinitrophenol
| Thermogenin (brown fat)
240
Uncoupling agents act to
allow H+ to permeate the inner mitochondrial membrane
241
Cyanide inhibits the ETC at
complex IV (cytochrome a)
242
Lactate dehydrogenase catalyzes
pyruvate --> lactic acid (in low O2 environment)
| lactic acid --> pyruvate (in the liver)
243
Major carriers of nitrogen from tissues?
Alanine, Glutamine
244
What enzymes catalyze transamination rxns?
transaminases
245
Transaminases catalyze
transfer of nitrogen from an amino acid to alpha-ketoglutarate --> Glutamate
246
Alanine transaminase (ALT) catalyzes
alanine + a-ketoglutarate --> pyruvate + glutamate
247
Aspartate transaminase (AST) catalyzes
aspartate + a-ketoglutarate --> oxaloacetate + glutamate
248
What cofactor is required by all transaminases?
pyridoxal phosphate (Vit B6)
249
What are the major regulatory enzymes of the TCA cycle?
Citrate synthase, Isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase
250
HMP Shunt - main objective
make NAPDH
251
G6PD catalyzes
G-6-P --> Ribulose-5-P + 2 NADPH
252
NAPDH oxidase catalyzes
O2 ---> O2- (oxidative burst)
253
Superoxide dismutase catalyzes
O2- ---> H2O2 (oxidative burst)
254
Myeloperoxidase catalyzes
H2O2 --> HOCl (oxidative burst)
255
Chronic Granulomatous Disease - deficient
NADPH oxidase
256
Chronic Granulomatous Disease Sx
susceptibility to catalase (+) organisms (aspergillus & s. aureus)
257
Glutathione Peroxidase catalyzes
H2O2 --> H2O
| GSH ---> GSSG (oxidizes Glutathione to reduce Oxygen radical in RBC)
258
Glutathione Reductase catalyzes
GSSG --> GSH
| NAPDH --> NADP+ (uses NAPDH to reduce glutathione in RBC)
259
G6PD catalyzes
NAPD+ --> NADPH
| G6P --> 6PG (uses G6P to regenerate NADPH in RBC)
260
G6PD deficiency
can't regenerate NAPDH -> susceptible to reactive oxygen species -> hemolytic anemia
261
What histological features are seen in G6PD deficiency?
Heinz bodies + Bite cells
262
What drugs may precipitate hemolytic anemia in G6PD deficient pts?
Sulfonamides, Primaqine, Nitrofurantoin, Isoniazid, Fava beans, Dapsone, Chloroquine
263
Essential Fructosuria - deficiency of
Fructokinase
264
Essential Fructosuria - Sx
fructose in urine
265
Fructose Intolerance - deficiency of
Aldolase B
266
Fructose Intolerance - Sx
hypoglycemia, vomiting, hepatomegaly, jaundice
267
Galactokinase Deficiency - deficiency of
galactokinase
268
Galactokinase Deficiency - Sx
cataracts
269
Classic Galactosemia - deficiency of
galactose-1-phosphate uridyltransferase
270
Classic Galactosemia - Sx
cataracts, jaundice, hepatomegaly, failure to thrive, low IQ
271
Lactose Intolerance - deficiency of
Lactase
272
Lactose Intolerance - Sx
bloating, gas, osmotic diarrhea
273
Kwashiorkor cause
protein malnutrition
274
Kwashiorkor Sx
fatty liver, edema, anemia, skin lesions
275
Marasmus cause
total energy malnutrition
276
Heterochromatin
condensed & inactive DNA
277
Euchromatin
less condensed & active DNA
278
DNA methylation at CpG islands causes
repression of transcription (mute)
279
Histone methylation causes
mainly reversible repression (mute)
280
Unambiguous codon feature means
a codon codes for ONE a.a.
281
Degenerate codon feature means
many codons code for the same a.a.
282
Origin of replication begins at
a consensus sequence
283
Example of disease resulting from a missense mutation
Sickle Cell (valine replaces glutamic acid)
284
Example of disease resulting from a frameshift mutation
Duchenne muscular dystrophy
285
Splicing
snRNPs form lariat -> excision to release intron
286
Antibodies to snRNPs
Anti-Smith
| Anti-U1 RNP
287
Abnormal splicing example of disease
b-thalassemia
288
acceptor stem of tRNA
3' CCA
289
T-arm of tRNA
thymine, pseudouridine, cytosine
290
D-arm of tRNA
dihydrouracil
291
tRNA wobble
first 2 nucleotides are required for base pairing of mRNA
292
Post-translational trimming
removal of N- or C-terminus from propeptides
293
Chaperone protein
assists in protein folding
294
Heat-shock protein
chaperone protein in yeast that prevents denaturing by high temp
295
What proteins prevent G1-S transition?
p53 & hypophosphylated Rb
296
What cells remain in permanent G0?
neurons, skeletal & cardiac mm., RBCs
297
What cells are quiescent?
hepatocytes & lymphocytes
298
What cells are labile?
continuously dividing: bone marrow, gut epithelium, skin, hair, germ cells
299
RER is site of
synthesis of exported proteins & N-linked oligosaccharide addition
300
SER is site of
steroid synthesis & detoxification
301
What cells are rich in SER?
hepatocytes (detox) & adrenal cortex (steroid synth)
302
Free ribosomes are site of
cytosolic & organellar protein synth
303
What cells are rich in RER?
Goblet cells (mucus secretion) & plasma cells (Ab secretion)
304
What tags proteins for lysosomes?
mannose-6-phosphate
305
Golgi Protein Modifications:
Modifies N-oligosaccharide on Asparagine
| Adds O-oligosaccharide on Serine & Threonine
306
I-cell Disease - deficient
phosphotansferase -> decreased mannose-6-phosphate -> excretion of lysosomal enzymes
307
Signal Recognition Particle
cytosolic ribonucleoprotein -> sends proteins from ribosome to the RER
308
Absent Signal Recognition Particle results in
protein accumulation in the cytosol
309
COP-II vesicular trafficking protein
sends stuff from ER to Golgi to vesicles (ANTEROGRADE)
310
COP-I vesicular trafficking protein
sends stuff from Golgi to ER
| RETROGRADE
311
Peroxisome
degrades very-long-chain FAs & branched FAs & a.a.
312
Proteasome
degrades damaged or ubiquitin-tagged proteins
313
MT structure
heterodimers of alpha- & beta-tubulin w/ 2GTP bound
314
Dynein
moves stuff retrograde (toward negative stable end)
315
Kinesin
moves stuff anterograde (toward positive growing end)
316
Cilia structure
9+2 MT arrangement
317
Axonemal Dynein
links MTs in cilia -> differential sliding of MTs results in bending of the cilia
318
Kartagener Syndrome - defect
dynein arm -> immotile cilia
319
Kartagener Syndrome - Sx
Situs inversus
Bronchiectasis
Chronic sinusitis
Infertility, risk of ectopic pregnancy
320
Which drug directly inhibits the Na/K-ATPase?
Digoxin & Digitoxin (reduced Na/Ca-exchanger to increase [Ca]ic -> increased contractility)
321
Type I Collagen
Bone, skin, tendons, dentin, fascia, cornea
322
Type II Collagen
Cartilage, vitreous body, nucleus pulposus
323
Type III Collagen
Blood vessels
324
Type IV Collagen
Basement Membrane
325
Reduced production of Type 1 Collagen
Osteogenesis imperfecta type 1
326
Deficient Type 3 Collagen
Vascular type of Ehlers-Danlos
327
Antibodies to type IV collagen found in glomerular BM
Anti-GMB in
| Goodpastures Syndrome
328
Collagen is 1/3 made up of
Glycine
329
What proteins inactivate CDK-Cyclin complexes?
p21, p27, p57
330
Cyclins are degraded by
ubiquitin protein ligase
331
Cyclin D complexes w/
CDK4
332
CyclinD/CDK4 complex
phosphorylates Rb -> release from E2F (TF)
333
Nuclear Localization Signal is rich in
Proline, Arginine, Lysine
334
Preprocollagen
alpha chains of glycine & usually proline & lysine
335
Collagen Synthesis - Hydroxylation of
Proline, Lysine (Vitamin C required)
336
Collagen Synthesis - Glycosylation of
Hydroxylysine
337
Procollagen
d/t addition of Hydrogen & Disulfide bonds
338
Tropocollagen formed in ______ by
ECS by cleavage of Disulfide-rich terminals
339
Collagen Fibril formation is catalyzed by
Lysyl Oxidase-Cu2+
340
Lysyl Oxidase-Cu2+ catalyzes
covalent cross-linkage of Lysine & Hydroxylysine for collagen fibril formation
341
Scurvy - pathogenesis
Inability to hydroxylate Proline, Lysine d/t deficiency in Vitamin C
342
Scurvy - Sx
Poor wound healing, swollen gums, anemia, bleeding, petechiae, tooth loss
343
Menkes Disease - defective
Copper absorption/transport -> decreased Lysyl oxidase activity -> decreased collagen fibril synthesis
344
Menkes Disease - Sx
brittle "kinky" hair, growth retardation, hypotonia
345
Elastin is rich in
proline, glycine
346
Elastase
breaks down elastin
347
alpha-1-antrypsin
inhibits elastase
348
Fibrillin
glycoprotein sheath that holds tropoelastin molecules together as elastin
349
Defect in Fibrillin
Marfan Syndrome
350
Marfan Syndrome - Sx
Hyperelastic joints, heart valve & aorta problems, aortic dissection, arachnodactyly, very tall, long arms & legs, pectus carinatum
351
Imprinting involves
methylation of one allele -> silenced
352
X-linked Dominant disorder
Hypophosphatemic rickets (phosphate wasting in PCT)
353
"Ragged red fibers"
Mitochondrial myopathies
354
Mitochondrial Inheritance disorders
Mitochondrial myopathies
355
Mitochondrial myopathies - Sx
myopathy, lactic acidosis, CNS disease
356
ADPKD - mutation in
PKD1 or 2 on chromosome 16
357
ApoB-48
found on chylomicrons for transport from enterocytes to lacteals
358
ApoB-100
found on VLDL, IDL, LDL for transport OUT of the liver; binds LDL receptor
359
ApoE
extra remnant uptake
360
ApoA-1
found on HDL, activates LCAT
361
LCAT
transfers cholesterol from peripheral tissues to HDL
362
CETP
exchanges cholesterol ester from HDL to LDL/VLDL/IDL in exchange for Triglycerides
363
ApoC-II
Cofactor for lipoprotein lipase
364
Hepatic lipase
modify IDL -> LDL of HDL-2 -> HDL-3 by removing TGs
365
SRB1
receptor on the liver for HDL-2/3 particles
366
Familial Hypercholesterolinemia - deficiency of
LDL receptors
367
Familial Hypercholesterolinemia - Sx
tendinous xanthomas, corneal arcus, accelerated atherosclerosis, MI in young pt
368
Hyperchylomicronemia - deficient
Lipoprotein lipase or ApoC2 (cofactor) -> inability to remove cholesterol & TGs from blood
369
Hyperchylomicronemia - Sx
pancreatitis, HSM, pruritic xanthomas
370
Hypertriglyceridemia
overproduction of VLDL
371
Rate-limiting step of fatty-acid synthesis
Acetyl-CoA carboxylase
372
Rate-limiting step of b-oxidation of fatty acid
carnitine acyltransferase-1
373
Rate-limiting step of ketone body synthesis
HMG-CoA synthase
374
Rate-limiting step of cholesterol synthesis
HMG-CoA reductase
375
Essential Amino Acids
```
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Leucine
Lysine
```
376
What a.a. is the precursor for Histamine?
Histidine
377
What a.a. is the precursor for Porphyrin?
Glycine
378
What a.a. is the precursor for NO?
Arginine
379
What a.a. is the precursor for GABA?
Glutamate
380
What a.a. is the precursor for S-adenosyl-methionine (SAM)?
Methionine
381
What a.a. is the precursor for Creatine?
Arginine
382
What a.a. is the precursor for melatonin?
Tryptophan
383
What a.a. is the precursor for Niacin?
Tryptophan
384
What a.a. is the precursor for Serotonin?
Tryptophan
385
What a.a. is the precursor for Melanin?
Phenylalanine
386
What a.a. is the precursor for Dopamine, NE, & Epi?
Phenylalanine
387
Rate-Limiting step of the Urea Cycle?
Carbamoyl phosphate synthase 2
388
Deficiency in Ornithine Transcarbamylase
orotic aciduria, high carbamoyl phosphate, hyperammonemia
389
Deficiency in Ornithine Transcarbamylase - Sx?
slurred speech, somnolence, vomiting, cerebral edema, blurred vision
390
Deficiency in Ornithine Transcarbamylase - Tx?
low protein diet +/- phenyl butyrate, Benzoate, Biotin
391
Phenylalanine hydroxylase catalyzes
phenylalanine --> tyrosine
392
Cofactor for Phenylalanine hydroxylase
BH4
393
Deficiency in Phenylalanine hydroxylase or BH4 cofactor?
PKU
394
Deficiency of Homogenisate oxidase
Alkaptonuria
395
Alkaptonuria Sx
homogentisic acid (brown) -> dark sclera, black urine, arthralgias
396
Alkaptonuria Tx
Vit C, avoid phenylalanine
397
Alpha-ketoacid hydrogenase deficiency
Maple Syrup Urine Disease
398
Branched chain a.a.?
Isoleucine, Leucine, Valine
399
Tyrosinase deficiency
Albinism
400
Decreased tryptophan d/t def neutral a.a. transporter?
Hartnup Disease
401
Phenylalanine hydroxlase deficiency
PKU
402
Cystathione synthase deficiency (or B6 cofactor def)
Homocysteinuria
403
Deficient COLA renal transporters?
Cystinuria
404
Deficient tetrahydrobiopterin (BH4)
PKU
405
Pellagra
low levels of Niacin (Vit B3)
406
Pellagra Sx
Dementia, Diarrhea, Dermatitis
407
Sweet smelling urine - deficient
alpha-ketoacid dehydrogenase
408
Musty smell
PKU
409
Black urine
Alkaptonuria
410
Lens dislocation
Homocysteinuria
411
Cystine stones
Cystinuria
412
PKU Tx
avoid phenylalanine, supplement tyrosine
| avoid breast milk
413
Fetal effects from mother w/ PKU?
brain damage "maternal PKU"
414
Iron deficiency
Microcytic anemia
415
Zinc deficiency
delayed wound healing, decreased body hair, hypogonadism, anosmia, dysgeusia (decreased smell & taste), rash around mouth, nose, eyes, anus, anorexia, diarrhea, growth retardation, impaired night vision, infertility
416
Lead Poisoning
hearing prob, low IQ, peripheral neuropathy, Lead lines, bluish lines on gingiva (Burtons), anemia, and pain, Basophilic stipling
417
Iron poisoning
hematemesis, abd pain, hypovolemic shock,
6-72 h: metabolic acidosis
2-8wks: scarring of GIT & obstruction
418
Mercury Poisoning
affects the kidneys & brian, acrodynia, and pain
419
Tx for Lead poisoning
Succimer, EDTA
| infant w/ severe poisoning: Dimercaprol
420
Decreased NADPH d/t lack of HMP enzyme
G6PD deficiency
421
Inherited tubular amino acid transported
Cystinuria, Hartnup Ds
422
Deficiency in homogentisic acid oxidase
Alkaptonuria
423
Blocked degradation of branched chain a.a.
Maple Syrup Urine Ds
424
Enzyme deficiency in Fructose intolerance
Aldolase B
425
Enzyme deficiency in Essential fructosuria
Fructokinase
426
Enzyme deficiency in Classic galactosemia
Galactose-1-phosphate uridyltransferase
