BC disease 1

• Protein misfolding
• Inherited, sporadic, and acquired forms
• Accumulation of protease resistant isoforms invade CNS 
• abormal prion can trigger refolding of normal prion
• no cure

• ataxia, dementia, paralysis, spongiform brain, plaques
• -amyloid plaques

• CJD, vCJD, Kuru, BSE
• creuzfeldt-jakob disease, mad cow, variable CJD

• PrPc- Nomal 40%
• PrSc- Abnormal Scrapie 45%\ 30%

Creutzfeldt-Jakob Disease

• most common prion disease
• sporadic and inherited

• linked to mad cow BSE
• most recent cases of prion diseases

• first prion disease
• people of New Guinea
• eating brain of the dead

Bovine Spongiform Encephalopathy

• Mad cow disease
• cattle fed sheep protein feed with infected scrapie sheep

• CO binds to the heme iron of Hb tigher than O₂
• stabalized Hb in the R form
• inhibites the delivery of O₂ to tissues
• treated with O2 administration

• unstable Hb structure
• increase affinity for O2
•  decrease affinity for O2
• or increasing rate of oxidation of the hem Fe²⁺ to Fe³⁺ (methemoglobin)

• reduced synthesis of the alpha or beta chain
• profound anemia

substitution of Glu by Val at aa #6 in the globin subunit

• creates hydrophobic patch
• patch is shielded in the R form
• conversion to the T form exposes patch
• causes deoxygenated Hb to polymerize into long fibers
• distors the RBC
• carriers may have protection from malaria

• connective tissue disorder
• can be benign or more serious
• possible bowel or arterial rupture

skin fagility, hyperextensibility, and hypermobility

mutations in the genes that code for collagen proteins and genes encoding enzymes responsible for generation of mature collagen fiber

• brittle bone disease
• teeth and hearing abnormalities
• mutations in collagen genes

• vitamin C (ascorbate) deficiency
• unable to form hydropolines
• unable to form interchain H+ bonds that form collagen triple helix

defective, weak collagen

Fe²⁺ , ascorbate (vit C), and alpha ketoglutarate

lack of hydroxylysines prevent proper formation of extracellular covalent cross links and glycosylation

• 50% of drugs are chiral
• cant assume R and S enantiomers react the same in the body
• single enantiomer drugs more effective

• elevated blood ammonia levels
• after 1st month of life

• mutation in gene coding for ornithine transcarbamylase for formation of urea
• mutant exyme has reduced substrate affinity
• only 10% effective

• non steroidal anti inflamitory drug
• vioxx, celebrex,

• NSAID which inhibits cyclooxygenase activity
• COX1-good- protexts gastrointest mucus Ile
• COX2-bad- inflammation Val
• vioxx only affects COX 2

• inability to form functional peroxisomes,
• prevents synthesis of plasalogens
• prevents mylenation

• infants typically mentally retarded
• lack muscle tone
• characteristic facial features,
• usually fatal

• muscle weakness after periods of activity
• usually improve during rest
• facial muscles

• autoimmune disease
• produce antibodies to nicotinic acetylcholine receptor
• antibodies interfere with the funtion or destroy the receptor at the neuromuscular junction
• prevents muscle contraction

• anticholineresterase agents- increase acetylcholine and improve neuromuscular transmission
• immunosupressive drugs

cobratoxin, bungaroo toxin, conotoxin and tubocurarine arrows

• inhibit or stimulate membrane transport proteins
• paralysis by blocking nicotinic acetylcholine receptors

• inhibits the Na+/K+ ATPase
• puple foxglove

• cardiotonic steroid
• increase the contractile force of the heart
• slows the rate of heart beat
• narrow theraputic index must be strictly controlled

treat angina -(chest pain due to restricted blood to heart)

• converted to NO in the body
• relaxes blood vessels
• reduces workload of the hear and decreases heart oxygen requirement

• relatively specific cGMP phosphodiasterase inibitor
• cGMP levels elevated for longer following NO release
• blood vessels remain relaxed
• blood flow increases

• reduces bp
• treats ED

• "insulin dependent" diabetes
• juvinile onset

• autoimmune
• destruction of  cells in pancreas that produce insulin

• adult onset
• non-insulin dependent

• deficiency or alteration in insulin receptor
• insulin insensitivity
• sometimes defective insulin- reuires insulin

• bacterium Vibrio Cholerae
• produce cholera toxin with enzymatic activity
• catalyzes the transfer of ADP-ribose moiety of an NAD+ molecule to an Arg of a Gs protein located in intestinal epithelial cells
• blocks GTPase activity
• G protein remains active
• adenylate cyclase remains active
• cAMP remain elevated
• activates PKA
• phosphorylates CFTR chloride channel
• Cl- ions flood into lumen

• diarrhea, dehydration
• fatal without rehydration
• CF carriers may be resistant

• bacterium Bordatella pertussis
• produces pertussis toxin
• catalyzes ADP riboslation of G proteins
• inhibition of Gi
• Cys is ribosylated
• increase cAMP
• not sure link to coughing

• bacterium Yersina pestis
• encodes a protein YoPH
• protein Tyr phosphatase
• dephosphorylates key proteins of the immune system
• disrupts cell signaling and prevents immune response