Lecture 11+12 Flashcards
mechanism of NO in the nervous system
- arginine is broken down into citrulline and NO
- NO activates guanylyl cyclase
- cyclic GMP activates PKA
what are the 3 ways glutamate can be formed in the Brain?
- From glutamine (deamination by glutaminase)
- From alpha KG + NH4 + NADPH
- transamination of alpha KG (glucose derived) (needs B6)
what is an agonist of the NMDA (glutamate) receptor
Phencyclidine (PCP)
hallucinogen in humans
tranquillizer in animals
formation of GABA
glutamate to GABA by Glutamate decarboxylase (PLP)
glial cells take up most of the GABA in the synapse (converts to glutamine)
treatment for epilepsy
associated with low GABA
GABA analogs
drugs that block GABA uptake
valproic acid inhibits GABA-T (prolongs effects)
Benzodiazepines
Ex: valium
barbiturates bind to GABA receptor – potentiates GABA → reduced anxiety
importance of B12 and neurotransmitter synthesis
needed to regenerate methionine, which can be used to form SAM
SAM methylate’s 3 times to form choline
choline is needed for ACh
Huntington’s disease
autosomal dominant (gain of function)
triplet repeat expansion disorder (polyglutamine)
leads to neuronal degeneration
Spinocerebellar ataxia
over 40 genes may lead to this disorder
most are triplet repeat expansion (CAG)
autosomal dominant
cerebellum, pons, medulla and spinal cord atrophy
Fragile X Syndrome
loss of expression of the X-linked FMR-1 gene (FMRP protein deficiency)
loss of synapse maintenance, abnormal brain development
have similar features to autism
CGG expansion
Fragile X Tremor and Ataxia Syndrome (FXTAS)
massive overexpression of FMR1 mRNA
adult onset ataxia
prion disease
change in the tertiary structure of the PRP protein that leads to pathology (lots of Beta sheets)
