Biochemistry Flashcards
Plasmalogens (etherlipids)
These glycerophospholipids, defined by a vinyl ether double bond at the sn-1 position, account for 20% of the myelin phospholipid mass (compared with 18% in the average human phospholipid mass). Here, 70% of the total phosphatidylethanolamine in white matter is plasmalogen, in contrast to only 5% in liver.
Myelin Development
During development of the human nervous system, myelination starts in the motor roots of the PNS (fifth fetal month) and is followed by myelination of the spinal cord and brain (CNS). The majority of myelin is assembled during the first two years of postnatal life, but myelination continues for 2–3 decades in the human cerebral white matter.
CNS Main Myelin Proteins
PLPs - highly hydrophobic, resistant to proteolysis
MBPs (family) - do not have a tertiary structure, hydrophilic, and form on the cytoplasmic surface of the myelin membrane
Anticipation
Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome.
How many neurological, neurodegenerative and neuromuscular disorders are caused by the trinucleotide expansion mechanism?
At least 40 neurological, neurodegenerative and neuromuscular disorders are caused by the trinucleotide expansion mechanism
Trinucleotide repeat expansion disease types
Large expansions out of coding sequence - fragile X syndrome (CGG repeat, 200 for full picture, mental retardation) and Friedrich ataxia
Modest expansions of CAG repeats in coding sequence - Huntington’s disease (DNA blood sample to diagnose, autosomal dominant with complete penetrance) and spinocerebellar ataxias
Amyloid plaque shows high levels of which metallic compounds?
Aluminium compounds
How does beta amyloid plaque affect synaptic transmission?
Binds to VGCC and NMDA, which increases intracellular calcium levels, and it also causes endocytosis of NMDA, which increases long-term depression and decreases long-term potentiation.
Which amino acid readily forms radicals in beta amyloid plaque?
Methionine, since the radicals are hydrophobic they can embed in PCM
How does tau become pathognomonic in AD?
Hyperphosphorylation
How Does The Light Phase Return To The Dark Phase?
- Inactivation of PDE
GTPase Accelerating Protein (GAP) interacts with the α-GTP subunit changing it to the inactive form T-
α-GDP) which ultimately inactivates the PDE. - Inhibition of Tranducin Binding with Rhodopsin
Rhodopsin kinase phosphorylates Ser and Thr residues in C terminus of R*. Arrestin protein, an inhibitor
binds to these phosphorylated residues and inhibits its interaction with transducin. - Regeneration of 11-Cis-Retinal
Cis retinal is regenerated from all trans retinal in the retinal pigment epithelial cells (RPE) isomerase. - Stimulation of Guanylate Cyclase
Low concentration of intracellular Ca2+ stimulates Guanylate cyclase which synthesizes cGMP from GTP
(GTP cGMP + Pi-Pi).
Order of light wavelengths
High to low: Red cone Green cone Rhodopsin PSB11 +Cl in MeOH Blue cone
Normal prion function structure
Protection from oxidative stress and copper metabolism, primary structure is the same as the abnormal form but it is the secondary structure that differs
PrPsc structural pathology
The normal protein has extensive α-helix structure; the toxic ‘rogue conformer’ has less helical structure and extensive b-sheet regions. These changes make the abnormal conformer more resistant to protease degradation and changes solubility and protein-protein interactions. Converting normal to abnormal forms requires breaking and making many hydrogen bonds. The abnormal (PrPsc) form is very stable and does not spontaneously change back to the normal form.
Mutation predisposing to vCJD
Individuals that express MM alleles (prion protein with methionine at position 129) are much more likely to become infected with vCJD than individuals with VV prion genes (valine at this position). This may be because methionine residue at this position assists in protein-protein interactions with bovine infectious prion particles.
