Metabolic functions of the liver Flashcards

1
Q

What metabolism occurs in the liver?

A
  • Regulation of carbohydrate metabolism
  • Regulation of fat metabolism
  • Regulation of protein metabolism
  • Cholesterol synthesis and excretion
  • Synthesis of specialized molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What does the regulation of carboydrate metabolism do?

A

To maintain blood glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is involved in fat metabolism?

A

-Synthesis
-Beta oxidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is involved in the regulation of protein metabolism?

A

– Plasma protein synthesis
– Detoxification of ammonia - Urea formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is involved in the synthesis of specialised molecules?

A

-Bile acids
-Haemin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Where does the liver receive blood from and via what vein?

A

receives blood from the
gastrointestinal tract via the portal
vein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where does the liver empty its blood into and what does this ensure?

A

-Empties directly into major vessel
entering the heart.
-Ensure rapid circulation of its
products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where does the bile duct empty directly into and why?

A

Bile ducts empty directly into gut.
-Can rapidly influence the digestive
process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the 2 routes of the metabolism of ethanol?

A

– Oxidation through the activity of alcohol
dehydrogenase
– Microsomal oxidation using cytochrome P450

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is involved in the metabolism of ethanol, including enzymes and where it occurs?

A

-Cytosolic process
-Enzyme involved alcohol dehydrogenase
-Ethanol converted into acetaldehyde and NAD+ –> NADH + H+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the rate at which body metabolises alcohol?

A

Body metabolises approximately 10g of alcohol/hour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is methanol metabolised to?

A

Methanol is metabolised to formaldehyde

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is formaldehyde associated with?

A

Formaldehyde is very toxic and is associated
with blindness, paralysis and loss of consciousness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is involved in the metabolism of acetaldehyde including where it occurs and what enzymes are involved?

A

-Mitochondrial process
-Enzyme involved is aldehyde dehydrogenase
-Acetaldehyde converted into acetate and NAD+ +H20–> NADH + 2H+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens to the acetate formed in the metabolism of acetaldehyde and what enzyme is invovled?

A

Acetate–>Acetyl CoA
-Assisted by enzyme acetyl CoA synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What isoform of enzymes do caucasians have aldehyde dehydrogenase?

A

ALDH-1 and ALDH-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Km value comparison between ALDH-1 and ALDH-2

A

ALDH-2 has a lower Km than ALDH-1
-Therefore higher affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What enzyme do certain ethnic minorities only express and therefore what do they suffer from when consuming alcohol?

A
  1. Some only express less effective ALDH-1
  2. Suffer from with symptoms of vasodilatation,
    facial flush, tachycardia and nausea
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does microsomal ethanol-oxidising system(MESO) involve?

A

Involves the oxidation of ethanol by members of the cytochrome P450 family of enzymes

20
Q

What does the MESO pathway generate?

A

The pathway generates acetaldehyde?

21
Q

What does this system consume and hence what can this result in?

A

As this system consumes NADPH required for the
synthesis of the antioxidant glutathione it results in
increased oxidative stress

22
Q

What is the reactivity of acetaldehyde like and what can it inhibit?

A

Acetaldehyde is very reactive and can inhibit enzyme
function.

23
Q

What can acetaldehyde lead to in the liver?

A

In the liver this can lead to a reduction in the secretion of
both serum protein and VLDL

24
Q

What can acetaldehyde enhance production of and what can this lead to?

A

Can also enhance free-radical production – leading to
tissue damage such as inflammation and necrosis

25
Q

What is stage 1 of liver damage?

A

Fatty liver

26
Q

What is stage 2 of liver damage?

A

alcoholic hepatitis, groups of cells
die resulting in inflammation

27
Q

What is stage 3 of liver damage?

A

Cirrhosis which includes fibrosis,
scaring and cell death

28
Q

What cannot function as a cirrhotic liver and what can this result in?

A

As the cirrhotic liver cannot function
properly ammonia will accumulate resulting
in neurotoxicity, coma and death

29
Q

What does high NADH do to gluconeogenesis and what does this stimulate and cause?

A

High NADH inhibits gluconeogenesis and stimulates the
conversion of pyruvate to lactate leading to hypoglycaemia
and lactic acidosis

30
Q

What does high NADH do to fatty acid oxidation and what does this stimulate?

A

High NADH inhibits fatty acid oxidation and stimulates fatty
acid synthesis and the formation of triglycerides

31
Q

What does Acetyl CoA, NADH and ATP formed in ethanol metabolism inhibit and by inhibiting what?

A

Acetyl-CoA, NADH and ATP formed inhibit glucose
metabolism by inhibiting PFK and pyruvate dehydrogenase

32
Q

What cycle does NADH inhibit and what does this inhibit?

A

-TCA cycle and acetyl CoA
-This increases inhibition of glucose metabolism

33
Q

What does Acetyl-CoA result in the formation of?

A

Acetyl-CoA results in ketone body formation

34
Q

What are the 3 common phases involved in the metabolism of xenobiotics?

A
  1. Phase 1 oxidation
  2. Phase 2 conjugation
  3. Phase 3 elimiation
35
Q

What happens in Phase 1 in the metabolism of xenobiotics?

A

-Oxidation is the most common modification but also get hydroxylation and reduction
-Modification increases solubility
-These reactions are facilitated by cytochrome P450 enzymes

36
Q

Where is cytochrome P450 found organ and where exactly in cells?

A

Found mainly in liver and cells of the intestine
-In Endoplasmic reticulum

37
Q

What are P450 enzymes inducible by?

A

P450 enzymes are inducible both by their own
substrates (5-10 fold) but also related substrates (2-4 fold)

38
Q

What happens in phase 2 conjugation in the metabolism of xenobiotics?

A

Xenobiotic are modified by addition of groups
such as
* Glutathione
* Glucuronic acid
* Sulphate

39
Q

What does modification in phase 2 conjugation increase and do?

A

Modification with these groups increase
solubility and targets them for excretion

40
Q

What is aflatoxin B1 produced by?

A

Produced by the fungus
Aspergillus flavus

41
Q

What is aflatoxin activated by and what does this lead to?

A

Aflatoxin activated by
P450 isoenzymes leading
to epoxide formation and
hepato-carcinogenesis

42
Q

What do statins inhibit?

A

Statins inhibit HMG-CoA
reductase

43
Q

What are statins degraded by?

A

Are degraded by CYP3A4

44
Q

What activity does CYP3A4 activity inhibit and what does this do to Statin levels?

A
  • CYP3A4 activity inhibited by
    grapefruit juice
  • statin levels can rise by 15 fold
45
Q

What happens to modified compounds by the liver?

A
  1. Actively transported into bile and then into the intestines
  2. Fate of these molecules is the following:
    -Digestion
    -Excretion
    -Reabsorption via the enterohepatic circulation