First Aid:

Biochemistry:
Histones rich in lysine and arginine (positive charge)
H1 is linker DNA
Heterochromatin = Highly condensed (barr bodies inactive x chromosome)
Euchromatin is expressed
DNA methylation = cystosine and adenine are methylated in DNA replication
CpG methylation makes DNA MUTE
Histone methylation mostly makes DNA mute (reversible)
Histone acetylation makes DNA active
NucleoSide = base + sugar
NucleoTide = base + sugar + phosphate linked by 3-5 phosphodiester bond
5 end bears the triphosphate (energy source for the bond), triphosphate bond is
target of 3 hydroxyl attack
deamination of cytosine makes uracil, methylation of uracil makes thymine
deamination of adenine makes guanine
GAG amino acids necessary for purine- glycine, aspartate, glutamine
Disrupt pyrimidine synthesis:
leflunomide inhibits dihydroorotate dehydrogenase (carbamoyl phosphate +
aspartate -> orotic acid)
UMP synthase: orotic acid with PRPP to make UMP (impaired in orotic aciduria)
MTX, TMP, Pyrimethamine: inhibit dihydrofolate reductase (decrease dTMP) in
humans, bacteria, and protozoa
5-fu forms 5-F-dUMP which inhibits thymidylate synthase (decrease dtmp)

disrupt purine synthesis:

6-MP and its prodrug azathioprine inhibit de novo purine synthesis
Mycophenolate, ribavirin inhibit inosine monophosphate dehydrogenase

Disrupt purine and pyrimidine synthesis:

hydroxyurea: inhibits ribonucleotide reductase

ribonucleotide reductase: dADP and dATP negatively feedback and inhibit enzyme
Purine pathway rate limiting enzyme: PRPP amidotransferase, inhibited by AMP,
GMP, IMP, allopurinol, 6-MP
ADA deficiency: results in excess ATP and dATP, which negatively inhibit
ribonucleotide reductase in the synthesis of purine and pyrimidines for DNA
replication, decrease lymphocyte (SCID- ar)
Lesch-Nyhan disease: defective purine salvage, lacks HGPRT enzyme, XR
Increase cell breakdown, decrease renal excretion, monosodium urate crystals in
joints (negative birefringence- yellow when parallel)
Acute- colchicine or indomethacin, chronic due to decrease in renal excretion-
probenecid, chronic due to increase in breakdown- allopurinol

HGPRT acts via purine salvage pathway causes inhibition of PRPP synthase which
acts via de novo purine synthesis
In lesch-nyhan decreased hgprt removes the inhibitory effect on prpp synthase and
thus prpp synthase causes increase purine synthesis which worsens the condition
by causing increased levels of purines which get degraded via increased XO activity
thereby leading to hyperuricemia and precipitating gout
Methionine and tryptophan encoded by only 1 codon (aug and ugg)
Irinotecan/topotecan inhibit eukaryotic topoisomerase I
Etoposide/teniposide inhibit topoisomerase II
Fluoroquinolones inhibit topoisomerase II and IV
DNA polymerase III- 5 to 3 synthesis, and 3 to 5 exonuclease
DNA polymerase I excises RNA primer 5 to 3
Telomerase- an rna-dependent DNA polymerase that adds DNA to 3 ends of
chromosomes to avoid loss of genetic material with duplication
Frameshift mutation- duchenne muscular dystrophy, tay-sachs disease
Splice site mutation- retained intron in the mRNA protein with impaired or altered
function Beta thalassemia, dementia, epilepsy, cancers
Lac operon: low glucose- increase adenylate cyclase activity, increase generation of
cAMP and ATP, activation of catabolite activator protein- increase in transcription
High lactose- unbinds repressor protein from repressor/operator site- increase
transcription

Nucleotide excision repair: specific endonucleases release the oligonucleotides

containing damaged bases Occurs in G1 xeroderma pigmentosum
Mismatch repair: occurs in G2, defective in Lynch syndrome (hereditary
nonpolyposis colorectal cancer)
Base excision repair: glycosylase removes altered base, creates AP site, one or more
nucleotides are removed by AP-endonuclease (5) and lyase cleaves 3, dna
polymerase Beta fills the gap and dna ligase seals it . occurs through out the cycle

Nonhomologous end joining- defective ataxia telangiectasia, breast/ovarian cancers

with BRCA1 mutation and fanconi anemia
Enhancers and silencers may be located close to, far from or even within (in an
intron) the gene whose expression it regulates
RNA polymerase III makes 5S rRNA tiny
Alpha-amanitin- inhibits RNA polymerase II- severe hepatotoxicity if ingested
Rifampin inhibits dna dependent RNA polymerase in prokaryotes
mRNA stored in p-bodies for later translation
primary transcript combines with small nuclear ribonucleoproteins (snRNPs) and
other proteins to form spliceosome, lariat-shaped (looped) intermediate is
generated, lariat is released to precisely remove intron and join 2 exons
antibodies to snRNP (anti-smith) are highly specific for SLE and anti-U1-RNP
antibodies are highly associated with mixed connective tissue disease
microRNA are small, condensed, noncoding RNA molecules that
posttranscriptionally regulate gene expression by targeting 3 UTR of mRNA for
degradation or translational repression mutation can lead to malignancies
(silencing an mRNA from a tumor suppressor gene)
tRNA: 75-90 nucleotides, secondary structure
anticodon end is opposite 3
CCA is on 3 can carry amino acid
T-arm- ribothymidine, pseudouridine, cytidine
T-arm tethers tRNA to ribosome
D-arm-dihydrouridine- detects the tRNA by aminoacyl-tRNA synthetase

Chaperone protein- intracellular protein involved in facilitating and maintaining

protein folding- heat shock protein are expressed at high temperatures to prevent
protein denaturing/misfolding

Cyclins activate cyclin dependent kinases (cyclin-D and cdk4)

RB1 arrests cell in G1 phase, cdk4 phosphorylates RB1 causing cell to enter S phase
(if rb not phosphorylated the cell remains in G1 phase)
P53 inhibits cdk4 via p21 which prevents RB1 phosphorylation which provides time
for repair of damaged DNA
Mutations in tumor suppressor gene- li-fraumeni syndrome

Stable- enter G1 from G0 when stimulated hepatocytes, lymphocytes

Labile- never go to G0, short G1 divide rapidly- bone marrow, gut epithelium, hair
follicles, germ cells
Mucus secreting goblet cells of small intestine and antibody secreting plasma cells
are rick in RER
Site of steroid synthesis and detoxification of drugs and poisons-liver hepatocytes
and adrenal cortex and gonads are rich in SER
Golgi modifies N-oligosaccharides on asparagine, adds O-oligosaccharide on serine
and threonine
I-cell disease- defect in N-acetylglucosaminyl-1-phosphotransferase failure of golgi
to phosphorylate mannose residues on glycoproteins- proteins are secreted
extracellularly rather than delivered to lysosomes
SRP- traffics protein from ribosome to rer, if defective- proteins accumulate in
cytosol
Cop1- golgi to er (reverse)
COPII: CIS golgi- anterograde 2 step forward one step backward

Proteasome- barrel-shaped protein complex that degrades damaged or ubiquitin

tagged proteins PD

Microfilaments: muscle contraction, cytokinesis actin, microvilli

IMF- maintain cell structure- vimentin, desmin, cytokeratin, lamins GFAP,
neurofilaments
Microtubules: movement, cell division- cilia, flagella, miotic spindle, axonal
trafficking, centrioles
Vimentin- mesenchymal tissue (fibroblasts, endothelial cells, macrophages)
Dynein- retrograde to microtubule (+ to -) nucleus
Kinesin- anterograde to microtubules (- to +) periphery
Sodium potassium pump- pumpkin pump K in
Ouabain inhibits by binding to K+ site
Cardiac glycosides inhibit sodium potassium atpase which leads to indirect
inhibition of Na/Ca exchange increase in calcium in contractility
Type I- dentin, fascia, cornea, late wound repair
Type II: cartilage, vitreous body , nucleus pulposus
III- granulation tissue, reticulin- skin, blood vessels, uterus, fetal tissue
IV- basement membrane, basal lamina, lens
Glycosylation of pro-alpha chain hydroxylysine and formation of procollagen via
hydrogen and disulfide bonds (triple helix of 3 collagen alpha chains) problems
forming triple helix OI
Cleavage of disulfide rich terminal regions of procollagen- insoluble tropocollagen
problems with EDS
Cross-linking- lysine-hydroxylysine cross-link with lysyl oxidase- eds, menkes-
copper
OI: bite- bone fractures, blue sclerae, dental imperfections (t), ear- hearing loss
Menke- xlr- ATP7A

Gluconeogenic- met, val, arg, his

Influenza viruses are constantly evolving by reassortment of their genetic material. Mutations
cause minute changes in the hemagglutinin and neuraminidase antigens on the surface of the
virus. This change is gradual(increasing with each division cycle) and is called antigenic drift.
Since the strains produced by drift are somewhat similar to the older strains, some people are still
immune and some others will be partly immune (and get a milder illness).

It is due to this antigenic drift that a new vaccine has to be manufactured and reimmunization is
recommended each year.

In contrast, antigenic shift occurs when influenza viruses reassort. The virus acquires
completely new antigensfor example by reassortment between avian strains and human
strains. If a human influenza virus is produced that has entirely new antigens, everybody will be
susceptible, and the novel influenza will spread uncontrollably, causing a pandemic.