Biochemistry Flashcards
1
Q
Which enzyme does Leflunomide interrupt?
A
Dihydroorate dehydrogenase
2
Q
Which substance builds up with Leflunomide?
A
Carbamoyl phosphate
3
Q
Which process do Methotrexate, Trimethoprim, and Pyrimethamine interrupt?
A
Pyrimide synthesis
4
Q
How do Methotrexate, Trimethroprim and Pyrmethamine interrupt Pyrimidine synthesis?
A
Inhibit Dihydrofolate reductase
5
Q
Which enzyme does 5-fluorouracil (5-FU) interrupt?
A
Thymidylate synthase (block dUMP–>dTMP)
6
Q
Which molecule builds up when Dihydrofolate reductase is inhibited?
A
DHF
7
Q
Which process does 6-mercacptopurine interrupt?
A
Purine synthesis
8
Q
Which process do mycophenolate and ribavirin interrupt?
A
Purine synthesis
9
Q
Which enzyme do Mycophenolate and ribavirin inhibit?
A
Inosine monophosphate dehydrogenase (IMP builds up)
10
Q
Which substances disrupts both purine and pyrimidine synthesis?
A
Hydroxyurea
11
Q
Which enzyme does hydroxyurea inhibit? What builds up?
A
Ribonucleotide reductase, UDP
12
Q
Which enzyme is deficient in SCID?
A
Adenosine deaminase
13
Q
Adenosine deaminase is responsible for
A
Degradation of deoxyadenosine and adenosine into inosine
14
Q
What is the consequence of Adenosine Deaminase deficiency?
A
dATP accumulation, lymphocyte toxicity and death. Second most common cause of SCID
15
Q
Which enzyme is defective in Lesch-Nyhan syndrome?
A
HGPRT
16
Q
What is HGPRT responsible for?
A
Salvage purine pathway (AMP, IMP, GMP)
17
Q
Which molecules buildup in HGPRT deficiency
A
Hypoxanthine, Xanthine and Uric acid
18
Q
What is the function of Xanthine oxidase
A
Degrade hypoxanthine to xanthine, and xanthine to uric acid
19
Q
What is the treatment for Lesch-Nyhand syndrome?
A
Allopurinol or Fuboxostat
20
Q
What is the function of Allopurinol and Febuxostat
A
Inhibit Xanthine oxidase to decrease uric acid
21
Q
How is Lesch-Nyhan inhertied
A
XLR
22
Q
What are findings of Lesch-Nyhan
A
Hyperuricemia Gout Pissed off (aggression, self-mutilation) Retardation Dystonia
23
Q
What is the function of Probenecid
A
Increase secretion of Uric acid into Urine
24
Q
What does it mean when the genetic code is unambiguous
A
Each codon is specific for one amino acid
25
What does it mean when the genetic code is redundant
Each amino acid can be coded by multiple codons
26
Where is the TATA box located and what does it indicate
About 25bp upstream from promoter, origin of replication
27
Which DNA enzyme do fluoroquinolones inhibit?
Prokaryotic DNA Topoisomerase II (gyrase) and IV
28
Which DNA enzyme do Etoposide and Teniposide inhibit?
Eukaryotic Toposiomerase II
29
What is the function of DNA Polymerase III
Main prokaryotic replication enzyme. Synthesizes 5'->3'; proofreads 3' -> 5'
30
What is the function of DNA Polymerase I?
Prokaryotes only, degrades RNA primer and replaces with DNA (5->3 exonuclease)
31
Which enzyme is often dysregulated in cancer cells?
Telomerase
32
Which phase of the cell cycle does Nucleotide Excision Repair occur in?
G1
33
Which sorts of lesions does Nucleotide Excision Repair fix
Bulky helix-distorting lesions
34
Xeroderma pigmentosum results from a defect in which type of DNA repair mechanism?
Nucleotide Excision Repair
35
How is xeroderma pigmentosum inherited?
Autosomal Recessive
36
Standard clinical vignette of xeroderma pigmentosum patient
Severe sunburn when exposed to sun, multiple freckles on skin, painfully sensitive and bloodshot eyes, multiple cancerous eruptions on skin, increased risk of melanoma and squamous cell carcinoma
37
When does base excision repair occur?
Throughout cell cycle
38
What is base excision repair important for
Repair of spontaneous deamination
39
What are the enzymes involved in base excision repair?
DNA glycosylase, AP-endonuclease (cleaves 5' end), Lyase (cleaves 3' end), DNA Polymerase beta fills gap, Ligase seals
40
When does mismatch repair occur?
G2 phase of cell cycle
41
What syndrome does a defect in Mismatch Repair lead to?
Lynch syndrome (HNPCC)
42
What condition results from defective non-homologous end joining (double-stranded break repair)?
Ataxia telangiectasia; Fanconi syndrome
43
Which prokaryotic amino acid stimulates neutrophil chemotaxis?
N-formylmethionine (fMet)
44
Which part of a gene do RNA Polymerase II and multiple transcription factors sit
Promoter (TATA box, CAAT)
45
Name the polymerases that synthesize rRNA, mRNA and tRNA, respectively
RNA Polymerase I, II, III
46
Why is alpha-amanitin (found in Amanita philloides mushroom) toxic?
Inhibits RNA Polymerase II. Leads to severe hepatotoxicity
47
Which molecule does Rifampin target in bacteria?
RNA Polymerase
48
Which molecule does Actinomycin D target?
RNA Polymerase in both prokaryotes and eukaryotes
49
Which RNA processes occur in the nucleus?
Transcription
7-methylguanosine cap addition to 5' end
Polyadenylation to 3' end
Splicing of introns
50
Which RNA process occurs in cytoplasm prior to translation?
mRNA quality control at P-bodies (contain exonucleases, decapping enzymes and microRNAS; storage for future translation)
51
What are anti-Smith antibodies? Why are they important?
Autoantibodies against spliceosomal snRNPs. Highly specific for SLE
52
Which disorder are Anti-U1 RNP antibodies associated with
Mixed connective tissue disease
53
What is the function of microRNAs
Control protein expression by degrading or inactivating mRNA (decrease translation into protein)
54
Which end of a tRNA is anticodon located on?
3' end, CCA
55
What is the T arm of a tRNA
Ribothymidine, pseudouridine, cytidine sequence that binds ribosome
56
What is the D-arm of tRNA
Dihydrouridine residues necessary for tRNA recogition by correct amino-acyl tRNA synthetase
57
Which process initiates protein synthesis (ribosome binding)?
GTP hydrolysis
58
Which site of ribosome does initiation (methionine loading) take place?
P site
59
Describe elongation
Incoming aminoacyl-tRNA are in A site, P site accommodates growing peptide, E site holds empty tRNA to exit
60
What is the function of a chaperone protein
Maintain protein folding
61
What is the shortest phase of the cell cycle?
M (mitotic) phase
62
Which phases of the cell cycle are of variable duration?
G1 and G0
63
Explain how the cell cycle transitions each phase
CDKs are signaling proteins that must be activated by phase-specific cyclins at each phase. After forming a complex, Cyclin-CDKs phosphorylate other proteins
64
Describe the function of p53
Tumor suppressor gene. Induces p21 to inhibit CDK. Prevents transition from G1 to S if there are errors
65
Explain how Rb functions
Hypophosphorylated (activated) by p21. Binds and inactivates transcription factor E2F to inhibit progression to S phase.
66
Which cells are permanent and which phase of the cell cycle are they in?
Neurons, cardiac and skeletal muscle, RBCs. G0
67
Which cells are stable (quiescent) and which phase are they in?
Hepatocytes and lymphocytes; enter G1 from G0 when stimulated
68
Which cells are labile and which phase are they in?
Bone marrow, gut, skin, hair and germ cells. Never go to G0, divid rapidly with short G1. most affected by chemotherapy
69
What is the function of smooth endoplasmic reticulum?
Steroid synthesis and detox from drugs and poisons
70
Which cells would be rich in SER
Hepatocytes, adrenal cortex cells and gonadal cells
71
Which protein modification takes place on proteins designated to lysosome?
Mannose-6-phosphate addition
72
Which amino acid undergoes modification of N-oligosaccharides in the golgi?
Asparagine
73
Which amino acids under go addition of O-oligosaccharides in golgi?
Serine and Threonine
74
Which enzyme is mutated in I-Cell disease?
N-acetylglucosaminyl-1-phosphotransferase (NGAPT)
75
What is the etiology of I-cell disease?
Golgi cannot phosphorylate mannose residues, so enzymes designated for lysosome are secreted instead
76
What are the clinical features of I-cell disease?
Clouded corneas, coarse facial features, restricted joint movement, high levels of plasma lysosomal enzymes. Death in childhood
77
Dysfunction of which enzyme leads to protein accumulation in cytosol?
SRP (traffics proteins from ribosome to RER)
78
What is the function of COPI?
Retrograde vesicular transport from trans golgi to cis golgi and cis-golgi to ER
79
What is the most common mutation in Osteogenesis Imperfecta?
COL1A1/2, Type I Collagen
80
Clinical presentation of Osteogenesis imperfecta
multiple fractures, blue sclera, hearing loss, tooth decay
81
Defect in which collagen cause Vascular type Ehler Danlos syndrome
Type 3 collagen deficiency
82
Deficiency in which collagen type causes classical type (joint and skin) Ehler Danlos syndrome
Type V collagen
83
What is the most common type of Ehler Danlos syndrome
Hypermobility (joint instability) type
84
How is osteogenesis imperfecta inherited?
Autosomal dominant
85
Which protein is defective in Menkes disease?
ATP7A Copper transport protein
86
What is the etiology of Menkes disease
Impaired copper absorption and transport leads to decreased activity of lysyl oxidase
87
Clinical presentation and inheritance of Menkes disease
XLR connective tissue disorder that presents with brittle "kinky" hair, growth retardation and hypotonia
88
Which amino acids primarily compose elastin?
Proline, lysine, glycine
89
What is the defect in Marfan syndrome?
Defective fibrillin (glycoprotein that forms sheath around elastin)
90
What is the enzyme defect in emphysema?
alpha-1-antitrypsin (prevents elastase from breaking down elastin)
91
Which technique is useful for measuring gene expression?
Northern blot
92
Which test serves to confirm HIV after (+) ELISA
Western blot
93
How do Methotrexate, Trimethroprim and Pyrmethamine interrupt Pyrimidine synthesis?
Inhibit Dihydrofolate reductase
94
Which enzyme does 5-fluorouracil (5-FU) interrupt?
Thymidylate synthase (block dUMP-->dTMP)
95
Which molecule builds up when Dihydrofolate reductase is inhibited?
DHF
96
Which process does 6-mercacptopurine interrupt?
Purine synthesis
97
Which process do mycophenolate and ribavirin interrupt?
Purine synthesis
98
Which enzyme do Mycophenolate and ribavirin inhibit?
Inosine monophosphate dehydrogenase (IMP builds up)
99
Which substances disrupts both purine and pyrimidine synthesis?
Hydroxyurea
100
Which enzyme does hydroxyurea inhibit? What builds up?
Ribonucleotide reductase, UDP
101
Which enzyme is deficient in SCID?
Adenosine deaminase
102
Adenosine deaminase is responsible for
Degradation of deoxyadenosine and adenosine into inosine
103
What is the consequence of Adenosine Deaminase deficiency?
dATP accumulation, lymphocyte toxicity and death. Second most common cause of SCID
104
Which enzyme is defective in Lesch-Nyhan syndrome?
HGPRT
105
What is HGPRT responsible for?
Salvage purine pathway (AMP, IMP, GMP)
106
Which molecules buildup in HGPRT deficiency
Hypoxanthine, Xanthine and Uric acid
107
What is the function of Xanthine oxidase
Degrade hypoxanthine to xanthine, and xanthine to uric acid
108
What is the treatment for Lesch-Nyhand syndrome?
Allopurinol or Fuboxostat
109
What is the function of Allopurinol and Febuxostat
Inhibit Xanthine oxidase to decrease uric acid
110
How is Lesch-Nyhan inhertied
XLR
111
What are findings of Lesch-Nyhan
```
Hyperuricemia
Gout
Pissed off (aggression, self-mutilation)
Retardation
Dystonia
```
112
What is the function of Probenecid
Increase secretion of Uric acid into Urine
113
What does it mean when the genetic code is unambiguous
Each codon is specific for one amino acid
114
What does it mean when the genetic code is redundant
Each amino acid can be coded by multiple codons
115
Where is the TATA box located and what does it indicate
About 25bp upstream from promoter, origin of replication
116
Which DNA enzyme do fluoroquinolones inhibit?
Prokaryotic DNA Topoisomerase II (gyrase) and IV
117
Which DNA enzyme do Etoposide and Teniposide inhibit?
Eukaryotic Toposiomerase II
118
What is the function of DNA Polymerase III
Main prokaryotic replication enzyme. Synthesizes 5'->3'; proofreads 3' -> 5'
119
What is the function of DNA Polymerase I?
Prokaryotes only, degrades RNA primer and replaces with DNA (5->3 exonuclease)
120
Which enzyme is often dysregulated in cancer cells?
Telomerase
121
Which phase of the cell cycle does Nucleotide Excision Repair occur in?
G1
122
Which sorts of lesions does Nucleotide Excision Repair fix
Bulky helix-distorting lesions
123
Xeroderma pigmentosum results from a defect in which type of DNA repair mechanism?
Nucleotide Excision Repair
124
How is xeroderma pigmentosum inherited?
Autosomal Recessive
125
Standard clinical vignette of xeroderma pigmentosum patient
Severe sunburn when exposed to sun, multiple freckles on skin, painfully sensitive and bloodshot eyes, multiple cancerous eruptions on skin, increased risk of melanoma and squamous cell carcinoma
126
When does base excision repair occur?
Throughout cell cycle
127
What is base excision repair important for
Repair of spontaneous deamination
128
What are the enzymes involved in base excision repair?
DNA glycosylase, AP-endonuclease (cleaves 5' end), Lyase (cleaves 3' end), DNA Polymerase beta fills gap, Ligase seals
129
When does mismatch repair occur?
G2 phase of cell cycle
130
What syndrome does a defect in Mismatch Repair lead to?
Lynch syndrome (HNPCC)
131
What condition results from defective non-homologous end joining (double-stranded break repair)?
Ataxia telangiectasia; Fanconi syndrome
132
Which prokaryotic amino acid stimulates neutrophil chemotaxis?
N-formylmethionine (fMet)
133
Which part of a gene do RNA Polymerase II and multiple transcription factors sit
Promoter (TATA box, CAAT)
134
Name the polymerases that synthesize rRNA, mRNA and tRNA, respectively
RNA Polymerase I, II, III
135
Why is alpha-amanitin (found in Amanita philloides mushroom) toxic?
Inhibits RNA Polymerase II. Leads to severe hepatotoxicity
136
Which molecule does Rifampin target in bacteria?
RNA Polymerase
137
Which molecule does Actinomycin D target?
RNA Polymerase in both prokaryotes and eukaryotes
138
Which RNA processes occur in the nucleus?
Transcription
7-methylguanosine cap addition to 5' end
Polyadenylation to 3' end
Splicing of introns
139
Which RNA process occurs in cytoplasm prior to translation?
mRNA quality control at P-bodies (contain exonucleases, decapping enzymes and microRNAS; storage for future translation)
140
What are anti-Smith antibodies? Why are they important?
Autoantibodies against spliceosomal snRNPs. Highly specific for SLE
141
Which disorder are Anti-U1 RNP antibodies associated with
Mixed connective tissue disease
142
What is the function of microRNAs
Control protein expression by degrading or inactivating mRNA (decrease translation into protein)
143
Which end of a tRNA is anticodon located on?
3' end, CCA
144
What is the T arm of a tRNA
Ribothymidine, pseudouridine, cytidine sequence that binds ribosome
145
What is the D-arm of tRNA
Dihydrouridine residues necessary for tRNA recogition by correct amino-acyl tRNA synthetase
146
Which process initiates protein synthesis (ribosome binding)?
GTP hydrolysis
147
Which site of ribosome does initiation (methionine loading) take place?
P site
148
Describe elongation
Incoming aminoacyl-tRNA are in A site, P site accommodates growing peptide, E site holds empty tRNA to exit
149
What is the function of a chaperone protein
Maintain protein folding
150
What is the shortest phase of the cell cycle?
M (mitotic) phase
151
Which phases of the cell cycle are of variable duration?
G1 and G0
152
Explain how the cell cycle transitions each phase
CDKs are signaling proteins that must be activated by phase-specific cyclins at each phase. After forming a complex, Cyclin-CDKs phosphorylate other proteins
153
Describe the function of p53
Tumor suppressor gene. Induces p21 to inhibit CDK. Prevents transition from G1 to S if there are errors
154
Explain how Rb functions
Hypophosphorylated (activated) by p21. Binds and inactivates transcription factor E2F to inhibit progression to S phase.
155
Which cells are permanent and which phase of the cell cycle are they in?
Neurons, cardiac and skeletal muscle, RBCs. G0
156
Which cells are stable (quiescent) and which phase are they in?
Hepatocytes and lymphocytes; enter G1 from G0 when stimulated
157
Which cells are labile and which phase are they in?
Bone marrow, gut, skin, hair and germ cells. Never go to G0, divid rapidly with short G1. most affected by chemotherapy
158
What is the function of smooth endoplasmic reticulum?
Steroid synthesis and detox from drugs and poisons
159
Which cells would be rich in SER
Hepatocytes, adrenal cortex cells and gonadal cells
160
Which protein modification takes place on proteins designated to lysosome?
Mannose-6-phosphate addition
161
Which amino acid undergoes modification of N-oligosaccharides in the golgi?
Asparagine
162
Which test can be used to identify transcription factors and DNA binding proteins?
Southwestern blot
163
What is flow cytometry commonly used for?
Assess size, granularity and expression of proteins, especially in hematologic abnormalities and immunodeficiencies
164
Which test is useful for detecting single nucleotide polymorphisms and copy number variations in different genes
Microarrays
165
Which gene is mutated in Cystic Fibrosis?
CFTR on chromosome 7
166
Describe the etiology of cystic fibrosis
Misfolded CFTR protein not transported to membrane. Decreased Cl- reabsorption in skin and secretion in lungs and GI. Retained IC Cl- leads to increased Na+ and H2O reabsorption--> abnormally thick mucus secreted into lungs and GI tract.
167
What are pulmonary complications of cystic fibrosis?
Recurrent pulmonary (S. aureus) infections in infancy and adolescence (pseudomonas), chronic bronchitis, bronchiectasis
168
What are digestive complications in Cystic fibrosis?
Fat malabsorption, pancreatic insufficiency, steatorrhea, biliary cirrhosis, liver disease
169
Reproductive complications with Cystic Fibrosis
Men: Infertility due to absence of vas deferens
Women: Subfertility due to amenorrhea and abnormally thick mucus
170
What is the mutation in cri-du-chat syndrome?
congenital microdeletion of 5p
171
Clinical findings of Cri-du-chat syndrome
microcephaly, moderate to severe intellectual disability, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities (VSD)
172
What mutation occurs in Williams syndrome?
Deletion of 7q
173
What are clinical manifestation of William's syndrome?
Sunken nose bridge, short nose, "elfin" facies, intellectual disability, hypercalcemia (increased sensitivity to Vit D), well-developed verbal skills, extreme friendliness, CV problems
174
Describe CATCH 22 for 22q11 deletion syndromes
```
Cleft palate
Abnormal facies
Thymic aplasia (T cell deficiency)
Cardiac defects
Hypocalcemia secondary to parathyroid aplasia
```
175
What developmental defect do you get from 22q11 deletion?
Aberrant development of 3rd and 4th branchial pouches
176
DiGeorge Syndrome results from which mutation?
22q11 deletion
177
In Lesch Nyhan syndrome, activity of which enzyme is elevated?
PRPP amidotransferase
178
Which enzyme is involved in the committed step of de novo purine synthesis?
PRPP amidotransferase
179
What are the two effects of HGPRT mutation (Lesch-Nyhan)?
Increased de novo purine synthesis (increased PRPP amidotransferase activity) and increased uric acid production
180
How is Alkaptonuria inherited?
Autosomal Recessive
181
Which enzyme is deficient in Alkaptonuria?
Homogentisic Acid dioxygenase (tyrosine metabolism)
182
What are the symptoms of Alkaptonuria
adult-onset arthritis, blue-black deposits in sclera and ear cartilage
183
Which compound is in excess in Alkaptonuria?
Homogentisic acid
184
What are symptoms of arginase deficiency?
Progressive spastic diplegia, abnormal movements, growth delay and elevated arginine levels
185
Arginase is an enzyme in which metabolic cycle?
Urea cycle (produce urea)
186
What is the treatment for arginase deficiency?
Low-protein diet without arginine
187
Where are collagen alpha chains synthesized?
RER
188
Which part of collagen synthesis requires vitamin C?
Hydroxylation of proline and lysine in RER
189
Which condition leads to physical and mental retardation, megaloblastic anemia and elevated urinary orotic acid?
Hereditary orotic aciduria (defect in uridine 5'monophosphate synthase)
190
Metabolism of which amino acids produces propionyl CoA?
Valine, Isoleucine, Methionine, Threonine and odd-chain FAs
191
In breastfed infants that develop nausea, vomiting, tachycardia, hypotension, and hepatomegaly, suspect which disorder?
Galactose metabolism issues
192
Before alanine is converted to glucose, its amino group is converted to which molecule?
alpha-ketoglutarate
193
How does overdosing on Vitamin E affect adults and children, respectively?
Mortality from hemorrhagic stroke and necrotizing enterocolitis
194
What are two products of PPP?
NADPH (reductive reactions) and ribose-5-phosphate (precursor for nucleotide synthesis)
195
Which two enzymes are essential in the PPP for NADPH synthesis and ribose-5-P synthesis, respectively
G6PD and Transketolase
196
Which enzyme is involved in converting Fructose-6-p to ribose-5-p
Transketolase
197
Which enzyme converts Glucose-6-p to 6-PG
G6PDehydrogenase
198
How is methylmalonic acidemia inherited?
Autosomal recessive
199
Which enzyme is deficient in methylmalonic acidemia?
methymalonyl-CoA mutase
200
Which process is impaired in methylmalonic acidemia?
Breakdown of Valine, Isoleucine, Threonine, Methionine and odd-chain fatty acids to propionyl coA--> MMA--> Succinyl CoA (to enter TCA cycle)
201
how does methylmalonic acidemia lead to hypoglycemia
Increased metabolic rate leading to increased glucose utlization and direct toxic inhibition of gluconeogensis by organic acids
202
What causes ketosis and hyperammonemia in methylmalonyl acdiemia?
Free fatty acid metabolism and inhibition of urea cycle by organic acids
203
Presence of which urine compounds confirms methylmalonic acidemia in a neonate?
elevated urine methylmalonic acid and propionic acid
204
How does the body form ketones?
Metabolism of free fatty acids (beta oxidation in the mitochondria)
205
6-mercaptopurine and 6-thioguanine are activated and inactivated by
activated by HGPRT and inactivated by XO
