metabolic functions of the liver

Question 1

how does the liver lower blood glucose

Answer 1

by regulating flux into the pathways that remove free glucose

Question 2

what compounds does the liver receive from muscle

Answer 2

lactate and alanine

Question 3

how are alanine and lactate processed in the liver

Answer 3

both converted into pyruvate

glu-6-p > glucose which is transported to the muscle

Question 4

where are albumin and serum proteins mostly synthesised

Answer 4

the liver

Question 5

when especially does the liver degrade amino acids

Answer 5

gluconeogenesis

Question 6

how are AAs processed in the liver

Answer 6

deamination
transamination
detoxification

Question 7

sources of liver choleserol

Answer 7

de novo synthesis in the liver
dietary cholesterol - chylomicron remnants
cholesterol from extrahepatic tissue

Question 8

how does cholesterol leave the liver

Answer 8

free in bile
converted to bile acid
secretion of VLDL

Question 9

how is cholesterol synthesised in the liver

Answer 9

from acetyl CoA, using HMG-CoA reductase

Question 10

how is cholesterol transported from the liver

Answer 10

VLDL

Question 11

how is cholesterol secreted

Answer 11

biliary system as cholesterol or following conversion to bile acids

Question 12

what are the two routes of ethanol digestion

Answer 12

oxidation through alcohol dehydrogenase

microsomal ethanol oxidising system (MEOS_ on using cytochrome P450

Question 13

metabolism of alcohol in the cytosol

Answer 13

ethanol > acetaldehyde via NAD+ > NADH, H+

Question 14

alcohol metabolism in the mitochondria

Answer 14

acetaldehyde > acetate via NAD+ & H2O > NADH & 2H+

Question 15

what enzyme converts ethanol to acetaldehyde

Answer 15

alcohol dehydrogenasea

Question 16

what enzyme converts acetaldehyde to acetate

Answer 16

aldehyde dehydrogenase

Question 17

what does methanol get metabolised to

Answer 17

formaldehyde - toxic >paralysis, loss of consciousness, blindness

Question 18

why are large quantities of acetyl-CoA, NADH, and ATP formed from alcohol metabolism

Answer 18

oxidation of alcohol takes precedence over other nutrients

alcochol metabolism isn’t regulated by negative feedback

Question 19

how does alcohol metabolism inhibit the TCA cycle

Answer 19

high levels of ATP and NADH and NAD+ depletion inhibit TCA cycle

Question 20

how does ethanol oxidation lead to oxidative stress

Answer 20

microsomal oxidation by cytochrome P450 enzymes leads to oxidative stress

Question 21

how does excess alcohol metabolism cause fatty liver?

Answer 21

FA synthesis stimulated, as well as esterification to TGs to get exported as VLDL

Question 22

effect of acetaldehyde on the liver

Answer 22

reacts with/inhibits proteins - leads to reduction of secretion of serum protein and VLDL by the liver

Question 23

how can acetaldehyde cause inflammation and necrosis

Answer 23

by enhancing free radical production

Question 24

the 3 stages of liver damage

Answer 24

1 - fatty liver
2 - alcoholic hepatitis
3 - cirrhosis: fibrosis, scarring, cell death

Question 25

how can a cirrhotic liver be lethal

Answer 25

ammonia accumulates due to poor function, resulting in neurotoxicity, coma, and death

Question 26

what pathways are inhibited by ethanol metabolism

Answer 26

gluconeogenesis lactate > pyruvate FA > acetyl CoA TCA

Question 27

what are xenobiotics

Answer 27

compounds with no nutritional value

Question 28

phases of xenobiotic metabolism

Answer 28

1. oxidation 2. conjugation 3. elimination

Question 29

what is the point of xenobiotic oxidation

Answer 29

increases solubility | introduces functional groups for further reactions

Question 30

what promotes oxidation of xenobiotics

Answer 30

cytochrome P450 enzymes

Question 31

where are cytochrome P450 enzymes found

Answer 31

ER of liver and intestinal cells

Question 32

what type of proteins are CP450 enzymes

Answer 32

haem, related to the mitochondrial enzymes

Question 33

example of CP450 action

Answer 33

hydroxylation of ibuprofen

Question 34

what can induce CP450 enzymes

Answer 34

their own substrates AND related substrates

Question 35

what happens in conjugation of xenobiotics

Answer 35

``` modified by addition of groups like glutathione gluguronic acid sulphate - increases solubility and makes them a target for secretion ```

Question 36

what is the main action of statins

Answer 36

inhibit HMG-CoA reductase

Question 37

what degrades statins

Answer 37

CYP3A4

Question 38

what can inhibit CYP3A4

Answer 38

grapefruit juice

Question 39

what happens if you drink grapefruit juice while on statins

Answer 39

statin levels can rise by 15 fold because they're not degraded

Question 40

what is aflatoxin b1 activated by

Answer 40

P450 isoenzymes

Question 41

what is the result of aflatoxin b1 activation

Answer 41

epoxide formation and hepatocarcinogenesis

Question 42

what happens to modified compounds

Answer 42

now soluble - can be removed by kidney active transport into bile > intestines can be reabsorbed