FA Biochemistry Flashcards
1
Q
Orotic Aciduria
A
- inability to convert orotic acid to UMP
- increased orotic acid in urine; megaloblastic anemia (does not improve with B12 or folate); failure to thrive
Treatment: oral uridine administration
2
Q
Leflunomide
A
Inhibits dihydroorotate dehydrogenase
3
Q
Hydroxyurea
A
Inhibits ribonucleotide reductase
4
Q
Mycophenolate and Ribavirin
A
inhibit IMP hydrogenase
5
Q
6-Mercaptopurine (6-MP)
A
inhibits de novo purine synthesis
6
Q
5-fluorouracil
A
inhibits thymidylate synthase (decrease deoxythymidine monophosphate)
7
Q
Methotrexate
A
inhibits dihydrofolate reductase in humans
8
Q
Trimethoprim
A
inhibits dihydrofolate reductase in bacteria
9
Q
Pyrimethamine
A
inhibits dihydrofolate reductase in protozoa
10
Q
Adenosine deaminase deficiency
A
excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase –> prevents DNA synthesis
– dec lymphocyte could (major cause of autosomal recessive SCID)
11
Q
Fluoroquinolones
A
inhibit DNA gyrase (prokaryotic topoisomerase II)
– prevents bacterial division
12
Q
Transition Mutation
A
purine to purine
pyrimidine to pyrimidine
13
Q
Transversion Mutation
A
purine to pyrimidine
pyrimidine to purine
14
Q
Missense Mutation (+ example)
A
Nucleotide substitution resulting in changed amino acid.
Sickle cell disease
15
Q
Nonsense Mutation
A
Results in early stop codon
16
Q
Frameshift Mutation (+ example)
A
deletion or insertion of a number of nucleotides not divisible by 3 –> msireading of all nucleotides downstream
– usually results in non-functional protein
– throws off “commaless sequence”
Duchenne muscular dystrophy (deleted dystrophin): X Linked
17
Q
Mismatch Repair Disease
A
Lynch Syndrome (hereditary nonpolyposis colorectal cancer: HNPCC) - Autosomal Dominant
18
Q
Nucleotide Excision Repair Disease
A
Xeroderma Pigmentosum: prevents repair of pyrimidine dimers from UV light exposure
19
Q
Nonhomologous End Joining Disease
A
Mutated in ataxia telangiectasia:
- defects in ATM gene; breaks result in cell cycle arrest
Triad: cerebellar defects (Ataxia), spider Angiomas, and IgA deficiency
20
Q
Antibodies to spliceosome snRNPs
A
anti-Smith antibodies
highly specific for SLE
21
Q
anti-U1 RNP antibodies
A
highly associated with mixed connective tissue disorder
22
Q
Enzyme for Charging tRNA
A
Aminoacyl-tRNA synthetase
– attaches amino acid to CCA 3’ end of the rRNA
(CCA: Can Carry Amino acids)
23
Q
Cells rich in rER
A
Mucus-secreting goblet cells of the small intestine
Antibody-secreting plasma cells
— synthesis of secretory proteins
24
Q
Cells rich in sER
A
Liver hepatocytes
Steroid Hormone-Producing cells of the Adrenal Cortex and Gonads
– sites of steroid synthesis and detoxification of drugs and poisons
25
Peroxisome
catabolism of very-long-chain fatty acids, branched-chain fatty acids, and amino acids
(beta: oxidation: long-chain fatty acid degradation occurs in mitochondria)
26
I-cell disease
inclusion cell disease: inherited lysosomal storage disorder
- defect in phosphotransferase: failure of the Golgi to phosphorylate mannose residues (dec mannose-6-phosphate) on glycoproteins --> proteins secreted extracellularly rather than delivered to lysosomes
27
Proteasome (+ disease implication)
degrades damaged or ubiquitin-tagged proteins
| - defects in the ubiquitin-proteasome system have been implicated in some cases of Parkinson disease
28
Kartagener Syndrome
primary ciliary dyskinesia
- immotile cilia due to a dynein arm defect
- male (immotile sperm)and female (dysfunctional fallopian tube cilia) infertility
- cause bronchiectasis, recurrent sinusitis, and situs inversus
29
Histochemical Stain for Intermediate Filament: Vimentin
Connective Tissue
30
Histochemical Stain for Intermediate Filament: Desmin
Muscle
31
Histochemical Stain for Intermediate Filament: Cytokeratin
Epithelial Cells (keratinized)
32
Histochemical Stain for Intermediate Filament: GFAP
Neuroglia (Astrocytes)
33
Histochemical Stain for Intermediate Filament: Neurofilaments
Neurons
34
Type I Collagen
Bone (made by osteoblasts), skin, tendons;
late wound repair
dec production in osteogenesis imperfecta Type 1
35
Type II Collagen
Cartilage; vitreous body, nucleus pulposus
36
Type III Collagen
Reticulin: skin, blood vessels, uterus, fetal tissue, granulation tissue
Type III: Deficient in the vascular type of Ehlers-Danlos syndrome (ThreE D): this is NOT the common type of Ehlers-Danlos
37
Type IV Collagen
```
Basement membrane, basal lamina, lens
Glomeruli of kidney; capsule of lens
Under the FLOOR (basement membrane)
- Defect in Alport syndrome
- targeted by antibodies in Goodpasture Syndrome
```
38
Collagen Synthesis (inside fibroblasts)
1. Synthesis (RER): translation of collagen alpha chains (preprocollagen) - usually Gly-X-Y (with X and Y as prline and lysine)
2. Hydroxylation (RER): Hydroxylation of specific proline and lysine residues (requires vitamin C: deficiency -> scurvy)
3. Glycosylation (RER): Glycosylation of pro-alpha-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen alpha chains). Problems --> ostogenesis imperfecta
4. Exocytosis: of procollagen into extracellular space by Golgi
39
Collagen Synthesis (outside fibroblasts)
5. Proteolytic Processive: cleavage of disulfide-rich terminal regions of procollage, transforming it into insoluble tropocollagen
6. Cross-linking: reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by Cu2+ - containing lysyl oxidase) to make collagen fibrils. Problems with cross-linking --> Ehlers-Danlos
40
Ehlers-Danlos Syndrome
faulty collagen synthesis: hyperextensible skin, tendency to bleed (easy bruising), and hypermobile joints
- associated with joint dislocation, berry and aortic aneurysms, and organ rupture
41
Menkes Disease
connective tissue disease caused by impaired copper absorption and transport. Leads to dec activity of lysyl oxidase (copper is a necessary cofactor).
Brittle, kinky hair, growth retardation and hypotonia
42
Marfan Syndrome
defect in fibrillin-1 gene: glycoprotein that forms a sheath around elastin; AD
connective tissue disorder affecting skeleton, heart and eyes. Cystic medial necrosis of aorta --> aortic incompetence and dissecting aortic aneurysms; floppy mitral valve
43
Elastin
rich in proline and glycine: nonhydroxylated forms (difference from collagen)
- stretchy protein with skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava
- broken down by elastase (which is normally inhibited by alpha-antitrypsin)
44
Variable Expressivity (+ example)
Phenotype varies among individuals with same genotype.
2 patients with Neurofibromatosis Type I (NF1) may have varying disease severity. But they both express it to some degree
45
Incomplete Penetrance (+ example)
Not all individuals with a mutant genotype show the mutant phenotype.
BRCA1: do not always result in cancer
46
Pleiotropy (+ example)
one gene contributes to multiple phenotypic effects
| PKU: untreated phenylketonuria manifests with light skin, intellectual disability, and musty body odor.
47
Loss of heterozygosity (+ example)
if a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops
this is NOT true of oncogenes (gain of function mutations)
ex: retinoblastoma and the two-hit hypothesis
48
Dominant Negative Mutation
heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning
- mutation of a transcription factor in its allosteric site: nonfunctioning mutant can still bind DNA, preventing the wild-type TF from binding
49
Linkage Disequilibrium
tendency for certain alleles at 2 linked loci to occur together more often than expected by change
50
Mosaicism (+ example)
presence of genetically distinct cell lines in the same individuals: arises form mitotic errors after fertilization
- somatic mosaicism: mutation propagates through multiple tissues or organs
McCune-Albright syndrome: is lethal if the mutation is somatic but survivable if mosaic
51
Locus heterogeneity (+ example)
Mutations at different loci can produce a similar phenotype.
| Albinism can be caused by different mutations (melanin production or melanin transport)
52
Allelic Heterogeneity (+ example)
different mutations in the same locus produce the same phenotype. beta-thalassemia
53
Heteroplasmy
present of both normal and mutated mtDNA: resulting in variable expression in mitochondrial inherited disease
- the earlier the mutation occurs, the more cells that have the mutated DNA
54
Polygenic
group of non-allelic genes that together influence a phenotypic trait. Multiple factors; Multiple gene inheritance
examples: androgenetic alopecia (male pattern baldness)
55
Imprinting (+ example)
one allele is imprinted/inactivated by methylation. with one allele inactivated, deleted of the active allele --> disease
Prader-Willi and Angelman Syndrome
56
Uniparental Disomy
offspring receives 2 copies of chromosome from one parent and no copies from the other
- heterodisomy: indicates a meiosis I error
- isodisomy: indicates a meiosis II error
57
Prader-Willi Syndrome
maternal imprinting
Paternal gene is deleted/mutated and maternal gene is normally silent
- results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia
58
Angelman Syndrome
paternal imprinting
Maternal gene is deleted/mutated and gene from dad is normally silent
- results in inappropriate laughter (happy puppet), seizures, ataxia, and severe intellectual disability
59
Mitochondrial Myopathies
mitochondrial inheritance:
- myopathy, lactic acidosis and CNS disease
secondary to failure in oxidative phosphorylation
-- muscle biopsy shows "ragged red fibers"
60
Hypophosphatemic Rickets
inherited disorder resulting in increased phosphate wasting at proximal tubule
X linked dominant
61
Cystic Fibrosis
Autosomal Recessive mutation in CFTR (chr 7): Deletion of Phe508. Misfolded protein.
ATP-gated Cl- channel that secretes Cl- in lungs and GI tract and reabsorbs Cl- in sweat glands.
62
Duchenne Muscular Dystrophy
X-linked frameshift mutation (deleted dystrophin: DMD)
| - pseudohypertrophy of calf muscles
63
Becker Muscular Dystrophy
X-linked point mutation
| onset in adolescence or early adulthood
64
22q11 Deletion
CATCH-22
Cleft Palate; Abnormal Facies; Thymic aplasia (T cell deficiency); Cardiac defects; Hypocalcemia (secondary to parathyroid aplasia)
65
Kwashiorkor
```
protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty changes due to dec apolipoprotein synthesis)
- small child with swollen belly
results from protein deficient MEAL:
Malnutrition
Edema
Anemia
Liver (fatty)
```
66
Marasmus
total calorie malnutrition: tissue and muscle wasting, loss of subcutaneous fat and variable edema
Marasmus results in Muscle wasting
67
RDE: Glycolysis
phosphofructokinase-1
+ AMP, fructose-2,6-bisphosphate
- ATP, citrate
68
RDE: Gluconeogenesis
fructose-1,6-bisphosphatase
+ ATP, acetyl-CoA
- AMP, fructose-2,6-bisphosphate
69
RDE: TCA Cycle
isocitrate dehydrogenase
+ ADP
- ATP, NADH
70
RDE: Glycogenesis
Glycogen synthase
+ glucose-6-phosphate, insulin, cortisol
- glucose-6-phosphate, glucagon
71
RDE: Glycogenolysis
Glycogen phosphorylase
+ epinephrine, glucagon, AMP
- glucose-6-phosphate, insulin, ATP
72
RDE: HMP Shunt
glucose-6-phosphate dehydrogenase (G6PD)
+ NADP+
- NADPH
73
RDE: de novo pyrimidine synthesis
carbamoyl phosphate synthetase II
74
RDE: de novo purine synthesis
glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
- AMP, IMP (inosine monophosphate), GMP
75
RDE: Urea cycle
carbamoyl phsophate synthetase I
| + N-acetylglutamate
76
RDE: Fatty acid synthesis
acetyl-CoA carboxylase (ACC)
+ insulin, citrate
- glucagon, palmitoyl-CoA
77
RDE: Fatty acid oxidation
Carnitine acyltransferase I
| - malonyl-CoA
78
RDE: Ketogenesis
HMG-CoA synthase
79
RDE: Cholesterol Synthesis
HMG-CoA reductase
+ insulin, thyroxine
- glucagon, cholesterol
80
Hexokinase
most tissues; high affinity but low Vmax (capacity)
| - can work when there are tiny amounts of glucose
81
Glucokinase
liver only; most active post meal
| low affinity but high Vmax
82
Rotenone
inhibits Complex I of ETC
| causes dec proton gradient and block of ATP synthesis
83
Antimycin A
inhibits Complex III of ETC
| causes dec proton gradient and block of ATP synthesis
84
Cyanide
inhibits Complex IV of ETC
| causes dec proton gradient and block of ATP synthesis
85
Carbon Monoxide
inhibits Complex IV of ETC
| causes dec proton gradient and block of ATP synthesis
86
Oligomycin
inhibits Complex V of ETC (ATP synthase).
| No ATP is produced as the chain stops
87
Uncoupling Agents
increase permeability of mitochondria membrane: causing dec in proton gradient and inc O2 consumption. ATP synthesis stops but electron transport continues. Produces heat
88
Pleiotropy (+ example)
One gene contributes to multiple phenotypic effects. Untreated phenylketonuria: light skin, intellectual disability, and musty body order. Homocysteinuria is another.
89
Genetic Heterogeneity
mutation of different genes causes similar phenotype (this is NOT allelic heterogeneity: SAME locus/different mutation)
90
Allelic Heterogeneity
different mutation at the SAME locus produce similar phenotype (beta-thalassemia)
91
Locus Heterogeneity
same as genetic hetergeneity (mutation of different genes causes similar phenotype).
92
Polygenic
Polygene, multiple factor, multiple genes in inheritance. Group of non-allelic genes that together influence a phenotypic trait. Ex: androgenetic alopecia (male pattern baldness)
93
ApoA-I
LCAT activation (cholesterol esterification)
94
ApoB-48
Chylomicron assembly and secretion by the intestine
95
ApoB-100
LDL particle uptake by extrahepatic cells
96
ApoC-II
Lipoprotein lipase activation
97
ApoE3 and 4
VLDL and chylomicron remnant uptake by liver cells
