Boards Biochem Flashcards
1
Q
Chromatin
A
- Core struture of H2 with H1 not in core octomer. Increased H1 leads to increased more heterochromatin
- Contains positively charged amino acids Arginine and lysine.
2
Q
DNA Methylation
A
- Occurs on template strand during replication to C and A, contain ketone groups.
- Aids in mismatch repair
3
Q
Histone Methylation
A
Shuts down transcription
4
Q
Histone Acetylation
A
Increases Transcription
5
Q
Nucleotide demethylation
A
C-U demethylation is possible mutation
6
Q
Amino Acids Necessary for Nucleotide synthesis
A
-Glycine, Arginine, glutamate
7
Q
Purine Synthesis overview
A
- Begins with ribose-5P from HMP shunt then add ATP to make PRPP.
- PRPP goes through a number of steps to generate IMP which can then be converted to AMP and GMP
8
Q
Pyrimidine Synthesis Overview
A
- Begins with ribose-5P from HMP shunt then add ATP to make PRPP.
- PRPP added to orotic acid to generate UMP
- UMP converted to CTP
- UMP converted to dUMP through ribonucleotide reductase
- dUMP converted to dTMP through thymatidylate synthase and dihydrofolate reductase. (methyl group added)
9
Q
6 Mercaptopurine
A
Blocks Purine Synthesis
-activated by HGPRT and other steps in de novo purine synthesis
10
Q
Hydroxyurea
A
Blocks ribonucleotide reductase
-Inhibits synthesis of Uracil and Thymidine
11
Q
TMP
A
-Blocks Dihydrofolate reductase (Specifically in bacteria)
12
Q
SMX
A
-Blocks production of folate in bacteria (PABA)
13
Q
5-FU
A
Blocks thymidylate synthase
14
Q
Orotic Aciduria
A
Defect in UMP synthase in Pyrimidine Synthesis pathway
- Leads to accumulation of orotic acid and impaired pyrimidine synthesis
- Orotic Aciduria, Megaloblastic anemia that doesn’t correct with folate or B12, No changes in urea cycle. Autosomal recessive
- Tx: uridine summplementation
15
Q
Ornithine Transcarbamoylase
A
XR mutation in ornithine transcarbamoylase. Normally converts ornithine and carbamoyl phosphate into citurline
- Defect leads to accumulation of carbamoyl phosphate which is converted to orotic acid.
- Symptoms: Orotic aciduria, no megaloblastic anemia, reduced BUN and increased ammonia.
- Liver transplant is currative, argenine supplementation (impaired urea cycle is arginine sink), low nitrogen diet
16
Q
Purine Salvage Overview
A
- Adenosine is deaminated to inosine, GMP is converted to inosine for pool.
- Inosine and Guanine are converted to hypoxanthine, xanthine, and uric acid to be secreted.
17
Q
Adenosine Deaminase Deficency
A
- AR, Impaired ability to deaminate adenosine and turn to inosine. Causes increase in adenine andadensoine that inhibits ribonucleotide reductase leading to impaired synthesis and death of Lymphocytes
- A major cause of SCID
- Can be treated with gene therapy
18
Q
Lesch-Nyhan
A
- XR, defect in HGPRT. Normally HGPRT allows for hypoxanthine and guanine to feeback into inosine pool to be converted to Gaunosine and adenosine.
- Leads to impaired salvage, increased de novo production, and increased uric acid production
- Symptoms are Retardation, self mutilation, gout
19
Q
Allopurinol
A
Inhibits xanthine oxidase. Conversion of Xanthine to Uric acid.
-Used to treat gout
20
Q
Severity of mutations
A
-Silent<Frameshift
21
Q
RNA Pol I
A
-rRNA, increased in nucleolus
22
Q
RNA Pol 2
A
Binds to promote, AT rich region, and trancribes DNA
23
Q
RNA Pol 3
A
Transcribes tRNA
24
Q
Stop Codons
A
UAA, UGA, UAG
25
RNA processing
- Occurs in nucleus
- 5' 7 methylguanine cap
- Polyadenalation
- Splicing out introns (snRNP)
26
SnRNP
Aid in splicing
| -Can be a nidus for Lupus. Ab to DS DNA
27
Splicing Mutation Disease
Beta Thallesemia
28
tRNA Structure
Cloverleaf with many modified bases. AA binds to 3' OH
| -mRNA codon is read 5' to 3'. tRNA anticodon is read 3' to 5'
29
Charging
- Each tRNA is specific for a single AA. Determines the binding.
- Energy in tRNA-AA bond is enough to catalyze peptide bond formation
- ATP is the energy Source
30
Initiation of Protein Synthesis
Initiation factors bind ribosome and aid in assembly of ribosome and are released once mRNA binds.
31
Elongation
Charged tRNA binds to A site, and is moved to P site as the peptide bond is catalyzed by the ribosome
- tRNA leaves from the E site.
- GTP is the energy source for elongation
32
Termination
-Termiation signals involve releasing factors
33
Tetracyclines
- Bind 30 SPrevent binding of charged tRNA to acceptor site
34
Aminoglycosides
-Bind 30s and prevent initiation, Misreading leads to bacteriocidal activity
35
Macrolides
- Bind 50S and prevent tRNA from leaving the E site
| - Bacteriostatic
36
Cholramphenicol
-Bind 50S and prevent peptide bond formation
37
Fanconi Anemia
DNA repair defect, higher in jewish population
| -Presents with AML, birth defects and short stature
38
VHL
Muation in VHL gene that is an E3 ubiquitin ligase. Leads to elecated HIF-1alpha and a number of tumors
-Renal Cell Carcinoma (bilateral), Hemangiomas in brain and eyes, pheochromocytoma
39
Angelmann's Syndrome
- Only maternal allele is expressed, paternal is silenced via methylation
- If mutation in maternal exists then there is angelmanns
- Codes for a ubiquitin ligase
- Presentation: Developmental delay, ataxia, siezures, happy demeanor
40
RER
- Increased in secretory cells
- N linked sugars
- Synthesis, glycosylation, and hydroxylation of collagen
41
SER
Lipogenesis and detoxification
| -Increased in hepatocytes and steroidogenic cells
42
M6P
- Addition in golgi
| - Trafficks lysosomal proteins to the lysosome. Defect will lead to lysosomal storage disease
43
I cell Disease
- Impaired M6P leads to lysosomal storage disorder
- Elevated levels of lysosomal proteins in circulation
- Coarse Facial features, corneal clouding, joint restriction
44
COPI, COPII, Clathrin
COPI- Retrograde from Golgi to ER
COPII- Anterograde from ER to Golgi
Clathrin- endocytosis
45
Adrenoleukodystophy
-Defect in FA metabolism
| Demylination and adrenal insufficiency
46
Colchicine
Binds to tubulin dimers and prevents incorporation into MT
| -Used for gout
47
Vincristine/Blastine
- Binds to tubulin and prevents MT polymerization
- Used in Cancer
- Cristine causes peripheral neuropathy
- Blastine causes more bone marrow suppression
48
Paclitaxel
- Binds MT and stabalizes them, preventing depolymerization
- Cancer
- Myelosupression
49
Mebednazole
-Binds helminthic tubulin and prevents polymerization
50
Griseofulvin
- Binds fungal tubulin and prevents polymerization
| - P-450 inducer
51
Dyenin
-
52
Kinesin
+
53
Chediak Higashi
- Defect in LYST gene that is crucial for MT mediated vesicular sorting
- Results in partial albinism, recurrent pyogenic infections because of impaired intracellular killing, peripheral neuropathy
54
Karterengers
- Dyenein defect, impaired cilia
| - Situs inversus, Impaired fertility, Recurrent respiratory infections and bronchiectasis
55
Vimentin
CT
56
Desmin
Muscle
57
GFAP
Glia
58
Cytokeratin
Epithelium
59
Oubain
Inhibits Na/K ATPase
60
Digoxin
Inhibit Na/K ATPase which leads to secondarily impaired Na/Ca exchange. Leads to increased intracellular Ca and improved cardiac contractility
- CHF
- Overdose treatment: Lidocaine, K, Mg normalize and FAB to dig
61
Collagen I
Tendon, Skin, Bone
62
Collagen II
Cartillage
63
Collagen III
Reticular tissues: Granulation, BV, Fetal circulation
64
Collagen IV
Basement Membrane
65
Ehlers Danlos
Defect in typ 3 collagen
Joint hypermobility
increased risk for cerbral and aortic anyeurisms
66
Ehlers Danlos
Defect in typ 3 collagen. (other forms can exist, most sever is in 1 and 5)
Joint hypermobility, bleeding, easy bruising
increased risk for cerbral and aortic anyeurisms
67
Alports
type 4 collagen defect leading to impaired hearing and nephritic syndrome. May also be associated with vision loss
68
Collagen Synthesis
- Synthesis of polypepdtide backbone into ER. Contains gly-x-y, where x and y are commonly proline and lysine
- Hydroxylation of peptide in ER. Requires vitamin C most commonly proline and lysine residues
- Glycosylation of peptide occurs in ER. Commonly on lysine residues
- Glycosylated peptide forms triple helix (procollagen) with ends that are rich in disulfide bonds (cannot form fibrils due to end disulfide bond regions. Inability to form triple helix can result in OI.
- Procollagen exocytosed to ECM
- Procollagen end regions are cleaved, generating insoluble troppcollagen
- Insoluble tropocollagen peptides are crosslinked to form fibers and fibrils. Occurs by covalent binding of hydroxylysine residues, and is catalyzed by lysyl oxidase, an enzyme that requires Cu to function. Defects in cross linking result in Ehlers Danlos
69
Elastin
ECM component rich in proline and glycine
- Elastin is minimally if at all hydroxylated compared to collagen
- Major constiutent of elastic tissues (Blood vessels and lungs)
- Functions on a fibrilin scaffold
70
Elastin
ECM component rich in proline and glycine
- Elastin is minimally if at all hydroxylated compared to collagen
- Major constiutent of elastic tissues (Blood vessels and lungs)
- Functions on a fibrilin scaffold (Marfans)
- Elastase degrades elastin (inhibited by alpha 1 anti-trypsin)
71
Osteogenesis imperfecta
- Caused by a large variety of mutations (most commonly AD) in collage 1 that result in impaired triple helix formation
- Weak brittle bones with multiple breaks
- Blue sclera (blue is from visible venous drainage)
- Deafness due to breaks in ossicles
- Dental imperfections
72
Mafans
Mutation in Fibrilin gene, which normally sequesters TGF-B in ECF. Impairment leads to elevated TGF-B
- Tall and Long, pex cavus
- Lung problems and emphysema
- Lens dissolcation
- Mitral Prolapse, aortic anyerusism (most common cause death) and aortic regurg.
73
Alpha-1 antitrypsin
- Normally inhibits elastase and prevents elastin breakdown
- Mutation leads to alpha-1-antitrypsin defect and panacinar emphysema and cirrhosis (inclusions (PAS+ in ER) of misfolded alpha-1 antitrypsin
- Also smoking will destroy alpha-1 antitrypsin causing panacinar emphysema
74
Codominance
Blood Groups
75
Variable Expressivity
Everyone has disease but will have different severity
76
Incomplete penetrance
Genotypic mutation may not show phenotypic expression. BRCA. Disease skips a generation
77
Pleiotropy
Single mutation causing a number of unrelated symptoms
78
Imprinting
One parents copy is silenced, histone methylatoin. Mutation in a single gene will show effects
79
Angelmann
Maternal expressed. Mutation results in retardation, siezures, laughter.
80
Prader Willi
-Paternal Expressed. Hyperphagia, obesity, retardation
81
Loss Heterozygosity
TSG, two hit becomes one hit
82
Mosacism
-Post zygotic mutation (Sturge Webber)
83
Locus Heterogeneity
- Mutliple mutations can cause similiar symptoms
| - Marfanoid habitus with MEN, Marfans, homocysteinuria
84
Heteroplasmy
Mitochondrial DNA
85
Uniparental Disomy
- Meosis error resulting in 2 copies coming from a single parent.
- If Meiosis I error, chromosomes will be heterozygous
- If meiosis II error chromosomes will be homozygous (more serious)
86
Pedigrees
Circles are women
| Squares are men
87
X Linked Dominant
All Daughters of effected father will have disease
-Hypophosphatemic Rickets (impaired phosphate resorption in proximal tubule leads to phoshate wasting and rickets phenotype)
88
Mitochondrial
-Passed through Mother
-Mitochondrial Myopathies
Myopathy and CNS dysfunction. Ragged red fibers.
