Biochemistry Flashcards
1
Q
Codon that signals initiation of protein synthesis
A
AUG
2
Q
Stop codons
A
UAA
UAG
UGA
3
Q
Southern blot detects
A
DNA
4
Q
Northern blot detects
A
RNA
5
Q
Western blot detects
A
Protein
6
Q
Dot (slot) detects
A
RNA, DNA or protein
7
Q
Purine types and number of rings that they have:
A
Adenine
Guanine
2 rings
8
Q
Pyrimidines types and number of rings that they have:
A
Cytosine
Uracil
One ring
9
Q
A-T form __ bonds between them:
A
Two hydrogen bonds
10
Q
G-C form __ bonds between them:
A
Three hydrogen bonds
11
Q
Chemotherapeutic agents that target S phase:
A
Interfere with DNA Synthesis:
Methotrexate (ectopic pregnancy; dihydrofolate reductase, no thymine + leucovorin)
Capecitadine->5-flurouracil (pyrimidine analog, no thymine)
Cytarabine (AML; pyrimidine analog)
Clabribine (Hairy cell; purine analog). Claudio is a pure hairy man
Azathioprine->6-mercaptopurine (Ulcerative colitis; purine analog)
Hydroxyurea (ribonucleotide reductase)
12
Q
Chemotherapeutic agents that targets G2 phase:
A
Bleomycin (forms free radicals that breaks DNA)
Bortezomib
13
Q
Chemotherapeutic agents that target M phase:
A
Interfere with microtubules:
Vincristine
Vinblastine
Paclitaxel
Erlibutin
14
Q
Non cell-cycle specific chemotherapeutic agents:
A
Affect replication by: Alkaliting (cross link DNA): Cyclophosphamide (+ mesna) Cisplatin (+ amifostine) Busulfan (ablate marrow) Carmustine (glioblastoma) Procarbazine
Intercalating (intercalate within DNA chains):
Doxorubicin (+ dexrazoxane)
Daunorubicin (+ dexrazoxane)
Dactinomycin
15
Q
Chemotherapeutic agents that target the jump between S and G2 phase:
A
Etoposide, tenitopiside (inhibit topoisomerase 2)
Iridotecan, topotecan (inhibit topoisomerase 1)
16
Q
Eucromatine (from less to more condensed)
A
10 nm chromatin
30 nm chromatin
Loops of 30 nm chromatin attached to scaffolding proteins
17
Q
Is heterochromatin condensated or non condensated?
A
Highly condensed
18
Q
Leading strand characteristics:
A
Continuous
Moving into/ toward the replication fork
5’—>3’
19
Q
Lagging strand characteristics:
A
Discontinuos, series of Okazaki fragments
Moving away from the replication fork
3’—>5’ toward the replication fork
20
Q
Nalidixic acid mechanism of action:
A
It is a synthetic quinolone that inhibits DNA gyrase
21
Q
DNA polymerase gamma function:
A
Replicates mitochondrial DNA
22
Q
Single-stranded DNA-binding protein (SSB) function:
A
Stabilization of unwound template strands
23
Q
Fluorquinolones mechanism of action:
A
Inhibit tropoisomerases 2 (DNA gyrase) and 4
24
Q
Inactivation or deletion of p53 gene is associated with:
A
Li Fraumeni syndrome and solid tumors
SBLA: sarcoma, breast, brain, leukemia, adrenal
25
Most DNA repair occurs in ____ phase
G1
26
Which enzyme is deficient in xeroderma pigmentosa?
Excinuclease (excision endonuclease, an UV specific endonuclease) enzyme deficiency
27
Lynch syndrome (Hereditary nonpolyposis colorectal cancer) usually results from which mutation and which tumors are associated with it?
Autosomal dominant sd. due to a mutation in genes hML!!H1 and hMS!!H2! Love 1st Sex 2nd!
Increased risk of Colon (proximal colon is always involved), Endometroid (before 50), Ovary and STOMACH ca. CEOS of Merry Lynch
Dx: tumor cells on w. have microsatellite instability on GATA sequence on Ch7 (normally used for testing)
28
Mechanism of action of Rifampin:
Inhibiting prokaryotic RNA polymerase
29
Mechanism of action of Actinomycin D:
```
Chemotherapeutic drug (antitumor antibiotic) also called dactinomycin
Binds DNA to prevent transcription, it intercalates DNA
```
30
Alpha-amanitin (in certain mushrooms) acts
Inhibiting eukaryotic RNA polymerase 2!!
31
A cistron is
A gene
32
Hogness box
Pribnow box
are...
The TATA box
33
Two example sequences of promoter regions are:
```
CAAT box (80 bases upstream) and TATA box (25 bases upstream)
Binding site for general transcription factors and RNA polymerase 2
```
34
Missense mutation definition:
Change leads to a new amino acid
35
Nonsense mutation definition:
Change leads to a stop codon
36
Frame-shift versus in-frame mutation:
Frameshift: non triple number of nucleotides are deleted (Duchenne) or inserted (Tay-Sachs) so all aa after the mutation are messed up
In frame: nucleotide substitution (Becker) triplet deletion (CF) or insertion (Huntington, Spinobulbar muscular atrophy)
37
When does Gray baby syndrome occurs?
In babies with not enough UDP-glucuronyl transferase to metabolize chloramphenicol or inadequate renal excretion
If untreated they die from cardiovascular collapse
Chloramphenicol can also cause aplastic anemia and thrombocytopenia
38
Cystic fibrosis is normally consequence of
The deletion of phenylalanine at position 580 and generates improper folding
39
Klein-Waardenburg syndrome is due to
A mutation in a PAX gene
| Presents with partial albinism+deafness+aniridia
40
Menkes disease is due to
A deficient collagen cross-linking due to Cu deficiency (mutation in gene ATP7A)
41
Sensitivity and specificity of ELISA are:
Sensitivity: high
Specificity: low
42
Kwashiorkor is due to and presents with:
Protein malnutrition. Presents with edema
43
Marasmus is due to and presents with:
Chronic deficiency of calories. Does not present with edema
44
What do statins inhibit in cholesterol synthesis?
3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase
45
Name 4 facts about the action of Methotrexate
- Antineoplastic
- Interferes with DNA replication in phase S
- Competitively inhibits dihydrofolate reductase
- Deprives the cell of active folate
46
Competitive inhibitors effect in Km and Vmax:
Increase Km
| Do not change Vmax
47
Noncompetitive inhibitors effect in Km and Vmax:
Decrease Vmax
| Do not change Km
48
GLUT 1 and 3 have a ____ affinity for glucose
High
49
GLUT 2 has a ____ affinity for glucose
Low
50
GLUT 1 and 3 are in
Most tissues
51
GLUT 2 is in
The liver and pancreatic beta-islets
52
GLUT 4 is in
Skeletal muscle and adipose tissue
53
Pyruvate kinase deficiency is associated with
Ch1
Hemolytic anemia
Increased 2,3-BPG, low O2 affinity for Hb, high O2 in tissues
Burr cells (echinocytes)
No heinz bodies
Autosomal recessive ♂and♀ (DD. with G6PD that is X-linked ♂ recessive and will have heinz bodies)
54
Hexokinase/Glucokinase acts
In glycolysis
| Phosphorylating glucose to trap it in the cell
55
Heinz bodies are characteristic from
G6PDH deficiency
| Glutathione reductase deficiency
56
Galactosemia is due to a deficit of one of 2 enzymes:
Galactokinase or
| Galactose 1-phosphate uridyltransferase
57
Clinical picture of galactosemia:
```
Newborn
Cataracts
Jaundice
Hyperbilirrubinemia
Vomiting and diarrhea
```
58
Hereditary fructose intolerance is a deficiency of the enzyme:
Aldolase B
59
Clinical picture of hereditary fructose intolerance:
```
Starts when baby stops breast feeding
Vomiting
Lethargy
Liver damage, hyperbilirubinemia
Hypoglycemia
Hyperuricemia
Renal proximal tubule defect (Fancony)
```
60
Thiamine is
Vitamine B1
61
Thiamine (vit B1) deficiency may lead to
Beriberi
or
Wernike-Korsakoff syndrome (confusion, ataxia, ophthalmoplegia)
62
Clinical picture of Wernike-Korsakoff syndrome:
```
Alcoholic
Ataxia
Ophthalmoplegia, nystagmus
Memory loss and confabulation
Cerebral hemorrhage
```
63
McArdle disease is a deficiency of
Muscle glycogen phosphorylase
64
Clinical picture of McArdle disease:
Weak, initial exercise intolerance with cramps
Recovery or ‘second wind’
Possible myoglobinuria
No lactic ac. in venous blood
65
Pompe disease is a deficiency of:
Lysosomal alpha1,4-glucosidase
66
Clinical picture of Pompe disease:
Cardiomegaly
Muscle weakness
Death in 2 years
Due to accumulation of glycogen-like material in endosomes
67
Function of chylomicrons
Transport triglycerides and cholesterol from intestine to tissues
68
Function of VLDL
Transport triglycerides from liver to tissues
69
Function of IDL
Pick up cholesterol from HDL to form LDL
70
Function of LDL
IDL remnant, takes cholesterol from the liver to the peripheral tissues
71
Function of HDL
Takes cholesterol from peripheral tissues to the liver (reverse cholesterol transport)
72
Clinical picture of Medium Chain Acyl-Coa Dehydrogenase (MCAD) Deficiency:
Fasting hypoglycemia
Lethargy, coma
C8-C10 acyl carnitines in blood
Episodes after fasting/illness
73
Tay-Sachs disease is a deficiency of _____ and _____ is accumulated
Hexosaminidase A deficiency
Ganglioside GM2 accumulation
74
Gaucher disease is a deficiency of_____ and _____ is accumulated
Glucocerebrosidase deficiency
Glucocerebroside accumulation
75
Niemann-Pick disease is a deficiency of_____ and _____ is accumulated
Sphingomyelinase deficiency
Sphingomyelin accumulation
76
The most common disorder in the urea cicle is:
Ornithine transcarbamoylase deficiency
77
Phenylketonuria is a deficiency of:
Enzyme Phenylalanine hydroxylase
Or cofactor Tetrahydrobiopterin (BH4)
78
Clinical picture of phenylketonuria:
Musty odor
Mental retardation
Pale skin, eye and white hair
Pallor of cathecholaminergic brain structures
79
Alkaptonuria is a deficiency of the enzyme:
Homogentisate oxidase, that converts tyrosine to fumarate
80
Clinical picture of Alkaptonuria:
Urine becomes dark
Ochronosis (dark cartilage)
Arthritis
81
Maple syrup urine disease is a deficiency of:
Branched-chain ketoacid dehydrogenase enzyme
82
Clinical picture of maple syrup urine disease:
```
Urine smells like maple syrup
Mental retardation
Abnormal muscle tone
Ketones
Metabolic acidosis
Hyperammonemia because urea cycle is blocked
```
83
Homocystinuria is due to:
Cystathionine synthase enzyme deficiency or affinity loss (B6)
Methionine synthase= homocysteine methyl transferase=Methylenetetrahydrofolate reductase deficiency (B12, folic acid)
84
Clinical picture of homocystinuria:
```
Deep vein thrombosis
Atherosclerosis
Early stroke and MI
Ectopic lens (luxates down and in)
Marfan-like habitus (loose slender fingers)
Mental retardation
```
85
Pyridoxine is:
Vitamin B6
86
Orotic aciduria can be a deficiency of the enzyme ____ or ____
Ornithine transcarbamoylase or OTC (generates hyperammonemia). Carbamoyl phosphate accumulates and backs up to orotic acid. You cannot form citruline
Uridine monophosphate synthase or UMP synthase (generates megaloblastic anemia) because orotic acid accumulates
87
Lesch-Nyhan syndrome is a deficiency of ___ and the enz. ___ is overactive:
Deficiency of HGPRT enzyme (purine salvage)
You cannot form GMP and IMP so PRPP accumulates and you have an overactive PRPP amidotransferase (de novo purine synthesis)
88
Clinical picture of Lesch-Nyhan syndrome:
Orange crystals in diapers
Spastic cerebral palsy
Self mutilation
Hyperuricemia
89
Histone acetylation forms
Euchromatin; Acetylation makes the DNA Active
| Deacetylation is the opposite and mutes the DNA
90
Methylation of DNA forms
Heterochromatin; Methylation Mutes the DNA
Hypomethylation is little methylation
Hypermethylation is a lot of methylation
91
Mechanism of action of streptomycin:
Binds 30S ribosomal subunit impairing the initiation of protein synthesis
92
Tocopherol is vitamin
E
93
Galactosyl beta-1,4-glucose is also called
Lactose
94
RNA polymerase I mainly produces:
Ribosomal RNA
95
RNA polymerase II mainly produces:
Messenger RNA
96
RNA polymerase III mainly produces:
Transfer RNA
97
Tetracycline acts:
Binding to the 30S subunit of microbial ribosomes preventing the attachment of tRNA (prevents protein synthesis)
98
Previous administration to which drugs is needed to do a TB test in the treatment of rheumatoid arthritis:
TNF-α inhibitors:
```
Etarnercept
Infliximab
Adalimumab
Certolizumab
Golimumab
```
They can also cause drug-induced lupus
99
The enzyme defective in PKU is:
Phenylalanine hydroxylase
100
Mode of inheritance of Lech Nyhan disease:
X-linked recessive
101
Mode of inheritance of Marfan sd:
Autosomal dominant
102
The enzyme lysyl oxidase requires as a cofactor:
Cu
103
Coenzymes that pyruvate dehydrogenase need to work:
Tender Loving Care For Nancy:
Thiamine pyrophosphate (from thiamine)
Lipoic acid
Coenzyme A (from pantothenic ac)
FAD (from riboFlavin, B2 as FAD gives 2 ATPs)
NAD (from Niacin, B3 as NAD gives 3 ATPs)
104
Enzymes that require thiamine pyrophosphate (coming from thiamine, B1) to work:
Be APT for thiamine:
Branched chain ketoacid dehydrogenase (Val, Iso->propionyl-CoA; Leu->acetyl-CoA)
Alpha-ketoglutarate dehydrogenase (Alpha-KG->succinyl-CoA)
Pyruvate dehydrogenase (pyruvate->acetyl-CoA)
Transketolase (Ribose5-P->glycolysis)
105
3 main features of G6PD deficiency are:
Immunodeficiency
Heinz bodies
Hemolytic anemia
106
Adenyl cyclase is inhibited by:
The alpha part of the Gprot Gi
107
Liver phosphodiesterase is inhibited by:
Methylxanthines
108
Phosphofructokinase-2 is inhibited by:
Glucagon phosphorylation
109
Na/K ATPase is inhibited by:
Ouabain
| Digoxin
110
Effect of competitive inhibitors in the Linewaver-Bruk plot:
The lines cross
111
Effect of non-competitive inhibitors in the Linewaver-Bruk plot:
The lines don’t cross
112
Hypoglycemia + hypoketosis indicate:
Beta-oxidation defect (more frequently MCAD deficiency)
113
The ABC carboxylases (that need ATP, biotin (B7 raw🥚) and CO2 to work)
PAPa:
Pyruvate carboxylase (gluconeogenesis: pyruvate->oxalacetate)
Acetyl-CoA carboxylase (FA synthesis: acetyl-CoA->malonyl-CoA)
Propionyl-CoA carboxylase (FA oxidation: propionyl-CoA->methylmalonyl-CoA; VOMIT pathway)
114
Vitamin K depending enzyme:
Gamma-Glutamyl-carboxylase
115
Differential diagnosis between Hurler and Hunter disease:
On Hurler disease the is corneal clouding
116
Name the two obliged activators of enzymes:
Acetyl-CoA (for pyruvate carboxylase in gluconeogenesis)
| N-acetylglutamate (for carbamoyl phosphate synthetase I in the urea cycle)
117
Tender Loving Care For Nancy enzymes:
Pyruvate dehydrogenase
Alpha ketoglutarate dehydrogenase
Branched-chain Ketoacid dehydrogenase
118
Which 5 things generate propionyl-CoA:
```
VOMIT
Valine
Odd-chain fatty acids
Methionine
Isoleucine
Threonine
```
119
Black urine is an indicator of the illness:
Alcaptonuria
120
Pink/red urine is an indicator of the illness:
Porphyria
121
Brown urine is an indicator of the illness:
It is an indicator of hyperbilirubinemia
↑ urobilinogen: hemolysis (not unconjugated! because it is fat soluble)
↑ conjugated bilirubin: hepatitis, obstruction
122
Caramel/burnt orange urine is an indicator of the illness:
Maple syrup urine disease
123
Enzymes that require the coenzyme form of B12:
Methylmalonyl-CoA mutase (peripheral neuropathy-> subacute degeneration)
Homocysteine methyl transferase=methionine synthase (homocysteinemia and macrocytic anemia)
124
Enzymes that require the coenzyme form of folic acid:
```
Thymidylate synthase (macrocytic anemia)
Homocysteine methyl transferase (homocysteinemia)
```
125
Enzymes that require the coenzyme form of pyridoxine B6:
Cystathione synthase (homocysteinemia and homocystine in urine)
ALA synthase (sideroblastic anemia)
DOPA decarboxylase
ALT, AST
126
6 mercaptopurine mechanism of action:
Inhibits amidotransferase in purine synthesis
127
Direction of DNA synthesis:
5’ to 3’
128
Protein defective in Marfan sd:
Fibrillin-1 (an extracellular glycoprotein that acts as a scaffold for elastin)
129
Reaction catalyzed by light exposure in the skin:
Conversion of 7-dehydrocholesterol to cholecalciferol (vit D3)
130
Substances that bind a Janus kinase/STAT messenger system:
Growth hormone
Prolactin
Erythropoietin
And cytokines (interferon and interleukin)
131
What activates prot. kinase C?
IP3 (by increasing intracellular calcium) and DAG
132
Elements of the PIP2 (phosphatidylinositol) system:
```
Gq protein
Phospholipase C
IP3 (Ca2+)
DAG
Prot. Kinase C
```
133
The PIP2 (phosphatidylinositol) system is activated by:
Vasopressin
| Epinephrine (alpha 1)
134
Elements of the cAMP system:
```
Gs or Gi protein
Adenyl cyclase
cAMP (degraded by PDE)
Prot. Kinase A
CREB (at the gene level)
```
135
The cAMP system is activated by:
Glucagon
Epinephrine (beta->Gs)
Epinephrine (alpha 2->Gi)
136
Cytochrome P450 inducers:
Barb’s funny mom refuses greasy carb shakes: Phenobarbital (barbiturates), phenytoin, modafinil, rifampin, griseofulvin, carbamazepine, St. John’s wort
Alcohol (chronic)
137
Cytochrome P450 inhibitors:
Gee queen GRACE IS inhibit: Gemfibrozil, quinidine, grapefruit juice, ritoNAVIR (protease inhibitors), AZOLes, cimetidine, eryTHROMYCIN (macrolides except azithromycin), isoniazid, sulfanilamides
```
Alcohol (acute)
Amiodarone
Diltiazem, verapamil
Quinolones (ciproFLOXACIN)
SSRIs (fluoxetine)
Cyclosporine
```
138
Which are the only purely ketogenic aa?
Lysine and Leucine
139
Biochemical processes that occur within the mitochondria:
Beta-oxidation of FA
TCA cycle
Carboxylation of pyruvate in gluconeogenesis
Transcarbamylation of ornithine in urea cycle
140
Biochemical processes that occur within the cytoplasm:
Glycolysis
FA synthesis
Pentode-phosphate pathway
Urea cycle (except OTC)
141
Hallmarks of Tay-Sachs disease:
Psychomotor retardation, no splenomegaly
142
Hallmarks of Gaucher disease:
Crumpled paper inclusions, bone problems and pancytopenia
143
Hallmarks of Niemann-Pick disease:
Foamy bubbly macrophages and splenomegaly
144
Characteristics of riboflavin (B2) deficiency:
```
Cheilosis or stomatitis (cracking lips and mouth corners)
Glossitis (magenta tongue)
Seborrheic dermatitis
Eye changes
Rare
```
145
Drugs metabolized by cytochrome P450 (affected by inhibitors and activators):
Antiepileptics, theophylline, warfarin
146
Substances that bind intracellular receptors with DNA-binding domains; zinc fingers:
Steroid hormones: testosterone, estrogen, cortisol, aldo...
Thyroid hormone
Vit. A and D
147
Substances that bind ligand-gated ion channels:
Neurotransmitters (Ach, 5HT, NMDA, GABA)
148
Substances that bind a tyrosine kinase system:
Transmembrane TK receptor: Insulin and all growth factors (insulin-like GF)
Transmembrane receptor for JAK-STAT pathway: cytokines, INFs, PRL, poietins, GH!!!
Insulin and GF do not activate JAK-STAT and vice-versa!
149
Substances that bind a G-prot coupled receptor:
Epinephrine (Gq, Gi and Gs)
Glucagon (Gi and Gs)
Ca2+ to regulate PTH (Gq)
150
Which pathway is inhibited by ethanol metabolism?
Gluconeogenesis
151
Which is the most damaging free radical? Example of what generates it:
Hydroxyl (OH), generated by Fe
152
Which enzyme convents oxygen in superoxide (O2-) free radical?
NADPH oxidase
153
What are the 4 mechanisms of the body to get rid of free radicals?
Antioxidants vit A,C,E
Superoxide dismutase (for superoxide)
Glutathione peroxidase (for hydroxyl, especially in RBSs needs HMP shunt)
Catalase (for hydrogen peroxidase)
154
Where do you get exposed to carbon tetrachloride and what does it cause?
Dry cleaning industry
Causes fatty liver and necrosis
It is oxidized by P450 and becomes toxic causing free radical injury and lipid peroxidation
155
Cofactors needed for wound healing and why:
```
Vit C (needed for HYDROXYLATION of Pro and Lys of pro-collagen)
Copper (needed for cross-linking of pro-collagen)
Zinc (needed for collagen type 3—>1)
```
156
Last step of heme synthesis enzyme and location:
Ferrochelase converts protoporphyrin to heme adding Fe to it. It occurs on the mitochondria
157
Glycine is an important component of:
Collagen (Gly-X-Y); it creates "kinks" in the aa sequence that are needed to correctly form the SECONDARY structure
Heme (+ Succinyl-CoA)
158
Important role of Alanine:
Activates gluconeogenesis
159
When is Proline hydroxylation deficient?
In scurvy (no Vit C)
160
Phenylalanine and Tyrosine are important components of:
Catecholamines
Melanine
T3 and T4
161
Tryptophan is an important component of?
Serotonin
Niacin
Melatonin
162
Which aa becomes essential in PKU? And which one needs to be lowered?
Tyrosine and they need to eat less Phenylalanine (because phenylalanine-hydroxilase doesn’t work)
163
Lysine is an important component of:
Collagen (needs Cu for hydroxylation)
| Histones
164
Arginine is an important component of:
Urea and creatinine!! Pee!!
NO
Histones
165
Glutamate is an important component of:
GABA
Glutathione
Accepts NH3 and forms Glutamine to transport it
Incorporated in the first reaction of de novo pyrimidine synthesis (2ATPs, CO2 and glutamine)
166
Important role of Cysteine:
It has a sulfhydryl group that forms disulfide bounds which helps forming protein tertiary structure
Sulfhydryl group are deadly
167
How can you diagnose thiamine (B1) deficiency?
Baseline erythrocyte transketolase activity (assume in alcoholic or malnourished)
168
Where do the primers have to bind in PCR?
Both the forward and reverse primers have to bind to the 3’ sequence of both the coding and the template strand
169
Tissues that cannot use ketonic bodies as energy source:
RBCs and liver
170
What molecule attaches to misfolded proteins to promote their destruction?
Ubiquitin
171
Which enzyme converts NE to Epi in the adrenal medulla?
Phenylethanolamine-N-methyltransferase (PNMT)
| Upregulated by cortisol
172
Pellagra is due to a deficiency of which vitamin?
B3, niacin
173
Why do fibrates cause cholesterol gallstones?
Because they inhibit cholesterol 7alpha hydroxylase so decrease bile acid production
174
Enz. deficient and hallmarks of Von Gierke disease:
```
Glucose-6-phosphatase
Severe hypoglycemia (with hepatomegaly, high cortisol and hyperlipidemia)
```
175
Enz. deficient and hallmarks of Pompe disease:
Acid alpha 1,4-glucosidase on the lysosomes
| Cardiomegaly (also hypotonia, macroglossia and hepatomegaly)
176
Why do you get anticipation?
Due to a further expansion of trinucleotide repeats during SPERMATOGENESIS
177
What is the most frequent cause of homocysteinuria? Which aa becomes essential?
Cystathionine synthase deficiency
| Cysteine becomes essential
178
Which aa becomes essential in phenylketonuria?
Tyrosine
179
Clinical picture of lead poisoning:
```
High protoporphyrin
Abdominal pain
Constipation
Neurophychiatric symptoms
Microcytic anemia (basophilic stippling and ring sideroblasts)
Blue lines in gums
Lead lines in bone Rx
Wrist and foot drop
```
180
What enzyme in the body has reverse transcriptase activity?
Telomerase
181
Which enzyme is deficient in I cell disease? What it’s its function?
N-acetylglucosaminyl-l-Phosphotransferase
Phosphorylates manoses in lysosomal proteins so they go inside the lysosomes
182
Name 4 important X-linked recessive diseases:
Homozygous women are also symptomatic and Turner X0
Duchenne, Becker
Lesch-Nyhan
G6PD deficiency
Hemophilia A and B
```
Menkes
OTC deficiency
SCID due to IL2 receptor deficit
Red-green color blindness
Fabry, Hunter
Wiskott-Aldrich, Burton
Ocular albinism
```
183
Name 3 important X-linked dominant diseases:
Heterozygous women can be also symptomatic but milder (X inactivation)
Hypophosphatemic rickets (Vit D resistance)
Fragile X
Alport
Rett (retarded ataxic girls, boys die -de novo bc no kids-)
184
Name 4 important mitochondrial inherited diseases and their molecular basis:
```
Leber optic neuropathy
Leigh sd (subacute necrotizing encephalopathy)
```
Due to oxidative phosphorylation defects
MELAS (encephalopathy, lactic acidosis, stoke-like)
Myoclonic epilepsy with ragged red muscle fibers
Due to a tRNA defect
185
Substances to avoid in G6PD deficiency:
```
TMP/SMX
Nitrofurantoin
Floxacines (fluorquinolones)
Isoniazid
Dapsone
Quinine
Fava beans
```
186
Fabri disease is a deficiency of _____ and _____ is accumulated
Alpha-galactosidase A
Globotriaosylceramide/ ceramide trihexoside
187
Ilnesses due to splicing problems:
The problem is on the mRNA intron not in the coding exon
```
Tay Sachs (most frequently due to frameshift)
Gaucher
Beta-thalassemia
Lupus
Marfan
```
188
To which portion of the tRNA does the aa bind?
It binds to the CCA portion at the 3’ end
189
What vitamin abnormality can cause pseudotumor cerebri? What else can it cause?
Vit A toxicity
Also causes arthralgias, alopecia, dermatitis and hepatomegaly
190
Clinical picture of arginase deficiency:
Normally symptoms after an insult:
Spasticity
Unsteady gait
Vomiting
Low serum urea and high arginine
191
Clinical picture of I cell disease:
Coarse face
Gingival hyperplasia
Cloudy cornea
Problems moving joints, deformities and scoliosis
192
What is the function of the 5’ 7-methylguanosine cap of mRNA?
Needed to be recognized by initiation factors in the ribosome
193
What is the function of the 3’ poly A tail of mRNA?
Avoid mRNA degradation by ribonucleases and allow it to leave the nucleus
Gets inserted into AAUAAA sequence
194
Which enzyme is defective in McArdle's?
Muscle glycogen phosphorylase or myophosphorylase
195
Clinical picture and reaction involved in pyruvate kinase deficiency:
Hemolytic anemia with high 2,3-BPG
| Phosphoenolpyruvate cannot be converted to pyruvate so cells that rely on glycolysis like RBCs lyse
196
Clinical picture and reaction involved in pyruvate dehydrogenase deficiency:
Neurologic deficits, lactic acidosis, high alanine, X-linked.
Do not give glucose! Gets better with ketogenic diet (low carb, high FAT and ketogenic aa, thiamine, lipoid ac and carnitine)
Pyruvate cannot be converted to Acetyl CoA so it cannot go to Krebs cycle
197
Enzymes activated allosterically by AMP:
PFK-1 in glycolysis
| Glycogen phosphorylase in glycogenolysis
198
Enzymes activated by insulin:
Glucokinase and PFK-2 in liver glycolysis
Glycogen synthase in glycogenesis
Acetyl-CoA carboxylase in FA synthesis
HMG-CoA reductase in cholesterol synthesis
199
Enzymes activated by glucagon and Epi:
Glycogen phosphorylase in glycogenolysis
| PEP carboxylase in liver gluconeogenesis
200
Name 4 important autosomal dominant diseases:
```
Familial hypercholesterolemia (LDL receptor)
Neurofibromatosis type 1
Marfan
Acute intermittent porphyria
```
201
Enzymes inhibited by allopurinol:
```
Xanthine oxidase
PRPP amidotransferase (also inhibited by azatioprine=6-mercaptopurine)
```
202
What is the mutation in Marfan? and in Fragile X?
Marfan: FBN1 (bueno)
| Fragile X: FMR1 (Fragilex Mental Retardation)
203
What is the difference between variable expressivity and incomplete penetrance?
Variable expressivity patients with the same genotype present differently in incomplete penetrance some patients with the bad genotype are not sick at all
204
What aa is precursor of 5HT? and of Epi?
Tryptophan: 5TH
Tyrosine: DOPA, DA, NE, Epi
205
Function and cofactor for phenyetanolamine-N-methyltransferase:
Converts NE to Epi in the cytoplasm
Upregulated by cortisol
Needs SAM
206
What is pleiotropy?
When one mutation causes different problems in different organs like blue sclera and fractures in OI
207
Mode of inheritance of OI:
Autosomal dominant
208
What organs handle galactose? and fructose? What enzyme defect causes a lot and little problems in their metabolism?
Glactose: Liver and brain lactating mama; lactase =) =) kinase =) Gal 1P uridyltransferase =(
Fructose: Liver and kidney; kinase =) aldolase B =(
209
Cathecholamine synthesis pathway:
```
Phenylalanine
(Phenylalanine hydroxylase, THB)
Tyrosine
(Tyrosine hydroxylase, THB)
DOPA
(DOPA decarboxylase or aa decarboxylase, B6)
DA
(DA beta-hydroxylase, VitC/Cu)
NE
(Phenylalanine-N-methyltransferase, SAM)
Epi
```
Summary of cofactors
THB → THB → B6 → VitC/Cu → SAM
TTBCS teeete becese...
210
Name 3 uncouplers and explain their mechanism:
Allow electron flow and O2 consumption but uncouple it to ATP generation, give the energy as heat
2,4-DNP (Dinitrophenol)
High dose aspirin
Thermogenin in brown adipose tissue
211
Which cellular process is defective in xeroderma pigmentosum?
Nucleotide excision repair, G1
212
Which cellular process is defective in BRAC1 and what ca. generates?
Homologous recombination
Breast, ovarian and prostate
213
Which cellular process is defective in Lycnh sd. and what ca. generates?
Mismatch base repair, G2
If you cannot correct mismatched bases you get microsatellite instability
Colon (HNPCC), endometrium, ovary, stomach, brain and thyroid
214
Which cellular process is defective in ataxia-telangiectasia?
ATM gene 3 functions:
Check point detecting (p53) double-stranded breaks-> ca.
Serine/threonine kinase activity with MHEJ to repair the double-stranded breaks (nonhomologous end joining) and generate VDJ recombination-> lymphopenia
Old mytochondria death
215
Ways to activate and mute DNA:
Mute: DNA and histone methylation, histone deacetylation
Active: histone acetylation
Same for DNA and histones
216
What is deficient in hyperchylomicronemia?
LPL enz or it's cofactor in the lipoprotein Apo C2
217
What is deficient in hypercholesterolemia?
LDL receptors or it's ligand in LDL ApoB-100
218
What is deficient in abetalipoproteinemia?
ApoB-48 and ApoB-100
219
What part of Hb is affected in thalassemia? and in porphyria?
Heme in porphyria
| Globin in thalassemia
220
What is coding introns or exons?
Exons are coding introns are spliced out!
221
Examples of transcription factors (DNA-binding proteins) and which kind of proteins use to bind DNA?
Lipid soluble hormone receptors that display Zinc fingers to bind HRE
PPARs (peroxisome proliferator-activated receptors) that display Zinc fingers to bind CRE
The most common way to bind DNA is though Zn fingers, the exceptions are:
Water soluble hormones receptors ↑cAMP and bind to CREB that display Leucine zippers to bind PPREs. C-Jun and c-Fos also work tough leucine zippers
Inflammation activates NFkB that displays Rel domains that activate JAK-STAT to bind kB elements
During development we activate Homeodomain proteins (HoX, PAX) that display HeliX-turn-helix
222
Zinc deficiency may lead to:
```
Alopecia
Poor wound healing
Stomatitis
Low immunity
Hypogonadism
Anosmia
Cirrhosis
```
Associated with acrodermatitis enteropatica
223
Hyperamonemia can be a deficiency of the enzyme ____ or ____
Carbamoyl phosphate synthetase 1. You cannot from Carbamoyl phosphate
Ornithine transcarbamoylase or OTC. Carbamoyl phosphate accumulates and backs up to orotic acid. You cannot form citruline
224
Metabolic changes done by alcohol:
↑NADH so:
Lactic acidosis bc pyruvate converts into lactate
Blocks gluconeogenesis bc OOA goes back to malate
Ketoacidosis bc Acetyl-CoA goes into ketones rather than to TCA
Steatosis bc DHAP and Acetyl-CoA from glycolysis go to FA synthesis
225
Why do we need NADPH for?
Glutathione reProduction
FA and cholesterol Production
Oxidative burst
226
What is the best test to dx: triplet expansion, translocations, aneuploidy, inheritance patterns, large genes defects?
Southern blot/PCR: triplet expansion
FISH: translocations, microdeletions
Karyotype: aneuploidy, large deletions
Linkage: ancestry, marfan and congenital adrenal hyperplasia
Multiplex probe hybridization: genes that can be mutated in different sites like dystrophin
227
What are the functions of eukaryotic DNA polymerase δ, α, β, ε and γ?
Δ(δ) and α to make DNA. δ elongates the Okazaki fragments
β and ε to repair errors
γ mitochondrial DNA
228
Which DNA polymerases can degrade both thymine and demethylated thymine?
demethylated thymine=uracil=RNA
thymine=DNA
Just the ones that remove the primer:
DNA polymerase 1 in prokaryotes
RNAhase in eukaryotes
229
What is the AAUAAA sequence function?
Signal in the hnRNA for Poly(A)polymerase to add the poly A tail
230
What is the AGGU sequence function?
Signal at the hnRNA exon/intron junction for the spliceosome to splice
231
What is the TATA, CAAT or GC boxes function?
Signal at the promoter region of the DNA for GENERAL transcription factors to bind and start transcription
232
What is the response elements/enhancer regions function?
Signal at the DNA for SPECIFIC transcription factors to bind and start transcription
233
What is the TTAGGG sequence function?
Signal at the telomeres of chromosomes for telomerase to add DNA
234
Enzyme affected in lead poisoning and in sideroblastic anemia:
Both have ringed sideroblasts in the marrow (heme accumulates in mitochondria) and basophilic stippling in the smear (RNA aggregates)
Lead: inhibits ferrochelatase and ALA dehydratase
Sideroblastic: ALA synthase (rate limiting)
235
What vitamins do the dehydrogenases need to work?
```
Niacin B3
But:
Branched chain ketoacid dehydrogenase
Alpha-ketoglutarate dehydrogenase
Pyruvate dehydrogenase
That also require B1, B2, B3 and B5
```
Succinate dehydrogenase or complex 2 in e- transport chain needs B2 and does need B3
236
Which enzyme needs only B1 to work?
Trasketo1ase; is the one tested on an alcoholic because it is selective for B1 and because it is cytoplasmic and therefore in the RBCs (the others are mitochondrial)
237
What vitamin is needed for adding or removing CoA?
PEntothenic acid of B5
238
What vitamins do the carboxylases need to work?
Biotin B7, ATP and CO2
Acetyl-CoA carboxylase
Pyruvate carboxylase
Propionyl-CoA carboxylase
239
What is methyl-THF and how are its levels in B9 and B12 deficiency?
Unusable folate after it is used
↓ in B9 deficiency
↑ in B12 deficiency
240
What vitamin is needed for adding or removing methyl groups?
Cobalamin B12
241
Which vitamin deficiency gives you hemolytic anemia?
Vit E deficiency because it causes membrane damage leading to thorny RBCs and breakdown
Also neuropathy, ataxia and retinitis pigmentosum
242
Name 7 medical conditions with polygenic inheritance:
```
Androgenetic alopecia
Epilepsy
Glaucoma
HT
Ischemic heart disease
Schizophrenia
DM2
Spina bifida
```
*Here the recurrence risk depends on the number of affected relatives
243
Name 4 examples of transcription factors:
```
C-myc (Burkitt)
MYCL1=L-myc (lung)
N-myc (neuroblastoma)
C-jun
C-fos
CREB
```
244
Name the 9 hydrophobic essential aa:
```
Glycine (tiniest), proline (collagen)
Alanine (starvation)
Valine, leucine, Isoleucine (branched chain)
Phenylalanine, tyrosine (PKU)
Tryptophan (5-HT, niacin)
```
245
Name the 8 intermediate substrates in the Krebs cycle:
Citrate Is Krebs' Starting Substrate For Making Oxalacetate:
```
Citrate
Isocitrate
α-Ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
Oxalacetate
```
246
Glycogen regulation by hormones and substrates:
↑ Glycogen synthase:
Insulin (liver and muscle)
Glucose 6P
Cortisol
↓ Glycogen phosphorylase:
Insulin (liver and muscle)
Glucose 6P
ATP
↑ Glycogen phosphorylase:
Epi beta (liver and muscle) alpha 1 (only liver)
Glucagon (only liver)
Ca inside the m. (synchronization of exercise and energy)
↓ Glycogen synthase:
Epi beta (liver and muscle)
Glucagon (only liver)
247
Important roles of Aspartate:
Carries ammonia at the beginning of the urea cycle
| Incorporated in de novo pyrimidine synthesis
248
Which 3 compounds require tetrahydrobiopterin for their synthesis?
Tyrosine
DOPA, DA, NE, Epi; low DA leads to hyperprolactinemia
Serotonin
249
What type of mutation causes a temperature-sensitive repression of the tryptophan operon in E. coli?
Missense, are the only mutations that are mild enough that can be only apparent under certain environmental conditions, in this case are called conditional mutations
Mutants of Escherichia coli exhibiting temperature-sensitive repression of the tryptophan operon because of a MISSENSE mutation that alters the tryptophanyl transfer ribonucleic acid (tRNA) synthetase
250
Which aa is needed for collagen and elastin cross-linking? Why is cross-linking important?
Lysine (Lysyl oxidase and Cu make covalent lysine-hydroxylysine cross-linkage)
Cross-linking is needed for elasticity and reinforcement
251
Define positive and negative nitrogen balance:
Negative: CATAbolism; burns, injuries, fevers, Kawashkior, hypothyroidism, wasting and fasting. The amount of nitrogen excreted is greater than the amount ingested.
Positive: ANAbolism; growth, hypothyroidism, tissue repair, and pregnancy. The amount of nitrogen excreted is less than the amount ingested.
252
Which aa is a precursor for thyroid hormone?
Phenylalanine
253
Which type of mutation do you get with a single nucleotide or base deletion?
Frameshift mutation
254
Where is the receptor for the signal recognition particle?
On the RER; if there is a problem in the signal recognition particle protein accumulates in the cytoplasm and never goes to the RER
255
What is the clinical consequence of eating a lot of carrots?
Increased β-carotenes in the diet cause the skin to turn yellow (hypercarotenemia) but the sclera remains white (vs jaundice)
256
Name a possible mechanism of resistance to restriction endonuclases:
Hypermethylation; methylase methylates DNA making the DNA resistant to restriction endonucleases
257
Which enzyme becomes essential to make nucleotides in G6PD?
Transketolase
258
Define genetic polymorphism:
A single nucleotide substitution that is present in at least 1% of the population
259
Phases of collagen synthesis and illnesses that interfere with them (5):
Procollagen synthesis (impaired synthesis of osteoid by osteoblasts): Osteogenesis imperfecta and alport
Proline and lysine hydroxylation: Scurvy; ultimately essential for triple helix formation
Hydroxylysine glycosylation
Triple helix assembly by hydrogen bonds: Osteogenesis imperfecta
Exocytosis
Cleavage of N and C regions: Ehlers-DaNlos
Cross-linking by lysyl oxidase: Menkes and Ehlers-DaNlos
260
Reactions canalized by 21 alpha hydroxylase, 11 beta hydroxylase and 17 hydroxypregnenolone:
21: progesterone →11-deoxycorticosterone and 17-hydroxyprogesterone →11-deoxycortisol
11: 11-deoxycorticosterone →corticosterone and 11-deoxycortisol →cortisol
17: pregnenolone →17-hydroxypregnenolone and progesterone →17-hydroxyprogesterone
21 puts the 11
11 takes out the 11
17 puts the 17
261
What is the diagnosis of a kid with neurologic defects, high lactate and high alanine in blood?
What if he also has fasting hypoglycemia and ketoacidosis?
Pyruvate dehydrogenase deficiency, X-linked
Pyruvate carboxylase deficiency, autosomal recessive (rare)
262
Which mutations alter RNA or cDNA length?
ONLY Frameshift/In frame because nucleotides are deleted or inserted!!
Nonsense, missense, conservative or silent mutations do not affect mRNA or cDNA length because they are substitutions! some will affect protein length but not mRNA length!
263
What makes elastin elastic?
Cross-linking
264
How are proteins needed for apoptosis transcribed if you are breaking up the cell?
Internal ribosome entry site; the internal ribosome entry site sequence (in the 5'UTR) makes that the eukaryotic ribosome binds mRNA and translation can happen in the middle of the mRNA sequence
265
Steps on a PCR (6):
Heating (95deg) → Dematuration → Cooling → Primers binding → Re-warming (72deg) → DNA polymerase binds more DNA
266
How do you explain that a normal mom has a baby with achondroplasia?
90% of the mutations are DE NOVO, 10% are inherited
267
How do you calculate carrier frequency based on incidence?
q=√incidence
carrier frequency=2!!!!!pq
DO NOT FORGET THE 2
268
When does the nondisjunction that causes Down syndrome occur?
On anaphase 1 or 2 of meiosis
269
Which enzyme is missing in the zona glomerulosa preventing the synthesis of cortisol and androgen?
17-hydroxylase that catalyzes the conversion of progesterone →17-hydroxyprogesterone
270
Name the 8 intermediate substrates in the urea cycle:
Ordinarily, Careless Crappers Are Also Frivolous About Urination
Ornithine + Carbamoyl phosphate →Citrulline + Aspartate →Argininosuccinate - Fumarate →Arginine - Urea →Ornithine
271
Which DNA damage do ionizing and UV radiation cause?
Ionizing = free radical formation double stand DNA breaks, fixed by NONhomologous recombination (not working in ataxia-telangiectasia)
Non ionizing (UVB) = DNA damage by formation of pyrimidine dimers, fixed by NUCLEOTIDE excision repair (not working in xeroderma pigmentosum)
272
What is the mode of inheritance of both Friedreich ataxia and ataxia telangiectasia?
Autosomal recessive
Friedreich, chromosome 9. Hammer toes, sensory loss
Telangiectasia, chromosome 11. Inmunodeficiency
273
Which processes occur inside and outside the cell in collagen synthesis? In which illnesses are each of them defective?
Inside, RER:
Procollagen synthesis: Defective in osteogenesis imperfecta (impaired synthesis of osteoid=bone matrix by osteoblasts) and Alport
Proline and lysine HYDROXYLATION in porcollagen: requires Vit. C, defective in Scurvy; ultimately essential for triple helix formation
HYDROxylysine glycosylation=disulfide bond formation
Triple helix assembly by HYDROgen bonds: Osteogenesis imperfecta (impaired synthesis of osteoid=bone matrix by osteoblasts)
Outside:
CUTting of disulfide bonds, cleavage of N and C regions: Ehlers-DaNlos
CrOss-Linking of pro-collagen by lysyl oxidase: requires CU, defective in Menkes
274
Why is fructose metabolized faster than glucose and galactose?
Why to treat Von Gierke you can eat glucose and corn but NOT fructose or galactose?
Why to treat some gluconeogenesis diseases you can eat galactose?
Fructose is closer to pyruvate in glycolysis so it is metabolized and sends energy to the TCA cycle faster than glucose and galactose
Fructose and galactose require an intact Glucose-6-phosphatase to increase the glucemia therefore in Von Gierke you can eat glucose and corn but NOT fructose or galactose
Galactose enters gluconeogenesis at one of it's latest steps trough Galactokinase → Galactose 1-phosphate uridyltransferase. So you can have a gluconeogenesis disease where the hypoglycemia is corrected by eating galactose and not glycerol or fructose (because glycerol and fructose enter gluconeogenesis a lot later)
