Metabolic functions of the liver Flashcards
(21 cards)
What metabolic processes does the liver control?
Regulation of carbohydrate metabolism
Regulation of fat metabolism
Regulation of protein metabolism
Cholesterol synthesis and excretion
Synthesis of specialised molecules such as bile acids and haemin
Where does the liver receive blood from?
Portal vein from GI tract
Which major dietary nutrients does the liver deliver?
Proteins, carbohydrates
Not lipids
What are the two routes to metabolism of ethanol?
- Oxidation with enzyme alcohol dehydrogenase (ADH) (90% of ethanol)
- Microsomal oxidation using cytochrome P450
(10-20% of ethanol)
Approximately how much alcohol is metabolised per hour?
10g/hour
Metabolism of ethanol via ADH?
- Ethanol is converted to acetaldehyde via ADH. Converts NAD to NADH (occurs in cytosol)
- Acetaldehyde is converted to acetate. (occurs in mitochondria) NAD+H2O=NADH
What are the two isoforms of ADH?
ALDH-1 and ALDH-2(prevelant in caucasions)
Which isoform is more effective?
ALDH-2
Low km
What is NADH used for synthesis of ?
Glutathione
Glutathione acts as an antioxidant
How can acetaldehyde cause accumulation of fats
Acetaldehyde is very reactive and can inhibit enzyme
function.
In the liver this can lead to a reduction in the secretion of
both serum protein and VLDL
VLDLs are how the liver transports fats around body
What are the three stages of liver faliure?
- Fatty liver
- Alchol hepatitis, groups of cells die, resuling in inflammation
- Cirrhosis
Why does cirrohposis cause neurotoxcity, coma and death?
Cannot process ammonia so will accumulate
What percenatage of cirrhosis is due to alcohol?
75% of all cirrhosis is due to alcohol
25% of alcoholics develop cirrhosis
How does high ethanol metabolism cause hypoglycemia and lactic acidosis
High NADH produced
NADH:
-Inhibits gluconeogenesis
- stimulates conversion of pyruvate to lactate
Other consequences of high NADH?
-inhibits fatty acid oxidation and stimulates fatty acid synthesis
- Inhibits TCA cycle (acetyl coA inhibits further)
- Inhibits gluconeogenesis and stimulates pyruvate to lactate
What does acetyl coA result in?
Ketone body formation and the stimulation of fatty acid synthesis
What are xenobiotics ?
Compounds with no nutritional value
Such as
plant metabolites
synthetic compounds
food additives
agrochemicals
cosmetics
by-products of cooking etc
drugs
How are xenobiotics metabolised?
Made soluble by liver so can be disposed
Made harmless
Metabolised by liver
How many phases of xenobiotics metabolism?
– Phase I oxidation
– Phase II conjugation
– Phase III elimination
