metabolic functions of the liver Flashcards
how does the liver lower blood glucose
by regulating flux into the pathways that remove free glucose
what compounds does the liver receive from muscle
lactate and alanine
how are alanine and lactate processed in the liver
both converted into pyruvate
glu-6-p > glucose which is transported to the muscle
where are albumin and serum proteins mostly synthesised
the liver
when especially does the liver degrade amino acids
gluconeogenesis
how are AAs processed in the liver
deamination
transamination
detoxification
sources of liver choleserol
de novo synthesis in the liver
dietary cholesterol - chylomicron remnants
cholesterol from extrahepatic tissue
how does cholesterol leave the liver
free in bile
converted to bile acid
secretion of VLDL
how is cholesterol synthesised in the liver
from acetyl CoA, using HMG-CoA reductase
how is cholesterol transported from the liver
VLDL
how is cholesterol secreted
biliary system as cholesterol or following conversion to bile acids
what are the two routes of ethanol digestion
oxidation through alcohol dehydrogenase
microsomal ethanol oxidising system (MEOS_ on using cytochrome P450
metabolism of alcohol in the cytosol
ethanol > acetaldehyde via NAD+ > NADH, H+
alcohol metabolism in the mitochondria
acetaldehyde > acetate via NAD+ & H2O > NADH & 2H+
what enzyme converts ethanol to acetaldehyde
alcohol dehydrogenasea
what enzyme converts acetaldehyde to acetate
aldehyde dehydrogenase
what does methanol get metabolised to
formaldehyde - toxic >paralysis, loss of consciousness, blindness
why are large quantities of acetyl-CoA, NADH, and ATP formed from alcohol metabolism
oxidation of alcohol takes precedence over other nutrients
alcochol metabolism isn’t regulated by negative feedback
how does alcohol metabolism inhibit the TCA cycle
high levels of ATP and NADH and NAD+ depletion inhibit TCA cycle
how does ethanol oxidation lead to oxidative stress
microsomal oxidation by cytochrome P450 enzymes leads to oxidative stress
how does excess alcohol metabolism cause fatty liver?
FA synthesis stimulated, as well as esterification to TGs to get exported as VLDL
effect of acetaldehyde on the liver
reacts with/inhibits proteins - leads to reduction of secretion of serum protein and VLDL by the liver
how can acetaldehyde cause inflammation and necrosis
by enhancing free radical production
the 3 stages of liver damage
1 - fatty liver
2 - alcoholic hepatitis
3 - cirrhosis: fibrosis, scarring, cell death
how can a cirrhotic liver be lethal
ammonia accumulates due to poor function, resulting in neurotoxicity, coma, and death
what pathways are inhibited by ethanol metabolism
gluconeogenesis
lactate > pyruvate
FA > acetyl CoA
TCA
what are xenobiotics
compounds with no nutritional value
phases of xenobiotic metabolism
- oxidation
- conjugation
- elimination
what is the point of xenobiotic oxidation
increases solubility
introduces functional groups for further reactions
what promotes oxidation of xenobiotics
cytochrome P450 enzymes
where are cytochrome P450 enzymes found
ER of liver and intestinal cells
what type of proteins are CP450 enzymes
haem, related to the mitochondrial enzymes
example of CP450 action
hydroxylation of ibuprofen
what can induce CP450 enzymes
their own substrates AND related substrates
what happens in conjugation of xenobiotics
modified by addition of groups like glutathione gluguronic acid sulphate - increases solubility and makes them a target for secretion
what is the main action of statins
inhibit HMG-CoA reductase
what degrades statins
CYP3A4
what can inhibit CYP3A4
grapefruit juice
what happens if you drink grapefruit juice while on statins
statin levels can rise by 15 fold because they’re not degraded
what is aflatoxin b1 activated by
P450 isoenzymes
what is the result of aflatoxin b1 activation
epoxide formation and hepatocarcinogenesis
what happens to modified compounds
now soluble - can be removed by kidney
active transport into bile > intestines
can be reabsorbed
