Alcoholism Flashcards
How is fatty acid synthesis stimulated in alcoholism?
Lots of NAD+ reduced to NADH by ADH and ALDH.
Increased ratio stimulates FA synthesis and opposes degradation.
What evidence links CYP2E1 to liver pathology?
Mice lacking the enzyme are less susceptible to liver damage induced by ethanol.
Antibodies against CYP2E1 inhibit excess FR formation.
How can we demonstrate HER production in vitro?
Via spin trapping.
A transient radical (half-life too short for detection) interacts with diamagnetic reagent to form a more persistent radical.
Accumulates to [] allowing detection and identification by EPR spectroscopy.
How is it believed that chronic alcohol consumption affects mitochondria?
Sun et al (2016) showed that chronically ethanol-fed mice had reduced levels of mt biogenesis regulators e.g. TFAM and NRF1 which hypothesised may –> ROS.
How does TNF-a induce liver injury?
Stimulates collagen synthesis in hepatic stellate cells.
Stimulates endothelial cells to synthesise adhesion molecules.
What evidence implicates TNF-a and NOX in alcohol-induced liver injury?
Add a NOX inhibitor (diphenylene iodonium chloride) –> decreased HER production and ethanol-induced liver injury.
Ethanol-induced pathology blocked in TNF-a-RI KO mice but no decline in intensity of FR signals.
What evidence suggests that decline in antioxidants can be prevented in alcoholism?
Give vitamin E + ethanol –> attenuate decline in GSH.
Give Quercetin + ethanol –> declines in plasma TBARS.
Give grapeseeds + ethanol –> mild decline in MDA levels. Aww
