misc Flashcards

1
Q

H2O2 effect in proteins

A

H2O2 selectively oxidizes sulfhydryl groups of specific cystine residues, which are reversible and constitute a control mechanism of protein function

• Several targets

i. Protein tyrosine phosphatases (inactivates)
ii. Protein tyrosine kinases (activates)
iii. Small g proteins (activates GTPases)
iv. Transcription factor Nrf2 and NF-kB (activates)

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2
Q

list the enzymatic and non enzymatic detoxification

A

enyzmatic - sod, catalase, Glutathione peroxidase (also thioredoxins, Glutaredoxins, Peroxiredoxins)

non enymatic- Small molecules can act and antioxidants, reduced state can donate electrons to ROS to stabilize

Vitamin A, Vitamin E (lipid membrane), Vitamin C – cytosol , GSH

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3
Q

SOD

A

converts superoxide to hydrogen peroxide via a dismutase reaction
• Copper-zinc SOD (cytosol)
• Manganese SOD  mitochondria

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4
Q

o Catalase

A

primarily in the peroxisomes, catalyzes the direct decomposition of H2O2 to water

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5
Q

o Glutathione peroxidase

A

removed H2O2 by using it to oxidize another GSH – a thiol-containing peptide

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6
Q

o Thioredoxings o Glutaredoxins (Grx)

A

repair damaged oxdaitive damage to amino acid side changes

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7
Q

o Peroxiredoxins (Prx)

A

class of H2O2 scavengers located in the cytosol, mito, peroxisomes, nucleus

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8
Q

alcohol effects at cellular level

A

inhibits the function of neurons by reducing the ability to transmit or fire electrical impulses

Two of the best-known effects of alcohol are its actions on GABA and glutamate

–> increases activity at GABAa receptor (inhibitory), functions as positive allosteric modulator –> Opens channel allowing small anions (Cl-) to pass in and out of the cell  suppresses neuron firing

–> inhibit the activity of glutamate receptors, glutamate = excitatory, inhibition by alcohol leads to the reduction of neural activity

Long list of other synaptic effects

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9
Q

alochol effects on memeory

A

Loss of memory –> hippocampus (alcohol precvents the hippocampus from consolidating information that actually forms the memory), inhibits long term potentiation and neuogenesis (new memory formation)
o How does EtOH effect the hippocampus/new memory formation
o i. inhibits cell cycle – adult hippocampal neurogenesis (in dentate gyrus) is controversial (?)
o Apoptosis
 Oxygen radicals

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10
Q

etoh assay kit

A

Assay kit, measures concentrations of EtOH by a dichromate method, dichromate is reduced by ethanol to a blush chromic product, the intensity of the colour is a direct measure of the alcohol concentration

Stats - 2 sample t-test to measure the mean of two groups, measures if these differences could happen by chance (5% change level set). Standard deviation is the measure of the amount of variation of a set of values

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11
Q

phase 1

A

oxidation (via chytochrome p450), reduction, and hydrolysis, making drug more polar to ointerating polar functional groups

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12
Q

phase 2 metabolism

A

glucoronidation, acetylation, and sulfation, conjugations to increase water solubility

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13
Q

maternal genetic variable and FASD

A

Maternal ADH and ALDH are found to be developmentally protective by reducing maternal plasma concentrations and fetal exposure to ethanol and acetaldehyde.

In three strains of maternal mice with differing levels of ADH, increasing maternal ADH activities correlated with decreasing maternal plasma ethanol concentrations and decreased fetal abnormalities (94

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14
Q

evidence for role of NOX in FASD

A

in mouse embryos exposed to EtOH, DPi (no inhibitor) ethanol increased ROS formation, oxidative DNA damage, embryonic caspase-3 activation and apoptosis were blocked –> but did not show proof that it prevented morphological and functional abnormalities

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15
Q

head space gas chromatography

A

head space –> used for samples with volatile and non volatile compounds, heats them up so you are only processing the volatile compounds

flame ionizing detection –> common for gas chromatography, will detect ions formed during combustion in a flame generated by hydrogen, using electrodes a current is generated propotional to the orgnanic compound

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16
Q

SIMPLE - how ROS effects protiens, lipids and DNA differently

A

proteins –> loss of activity of complete denaturation, Lipids –> initiate lipid peroxidation,
DNA –> oxidative DNA lesions.

17
Q

evidence that its ROS damage to DNa and not protein or lipids

A

OUr studies –> Evidence that ROS damage to DNA and not other macromolecules  benzoapyrene treated transgenic p53 mice (tumor suppressor gene that facilitaites DNa repair) had increased teratogenesis 2.5 and 2.5 +/- and -/-

18
Q

ogg1/8-oxoG as a gtpase

A

ogg1 binds free 8-oxoG to form a complex, can interact with RAS family of GTPases, catalyzes the replcament of GDP with GTP

ex. K-RAS activates mpakkinase, erk1/2, and PI3kinase which will phsophoylate and activate nfkb

19
Q

nox role in LTP

A

NMDA-dependent LTP and synaptic plasticity involved Nox-derived
superoxide and Nox inhibition resulted in impaired memory formation

20
Q

role of NOX in neurogenesis

A

NOX primary ROS in neuronal stem cells

ROS-mediated proliferation of NSCs involve the phosphoinositide
3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase/ extracellular-signal-regulated
kinase 1/2 (MAPK/Erk1/2) pathways (