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Biochemistry > Liver detoxification and alcohol > Flashcards

Liver detoxification and alcohol Flashcards

1
Q

In what ways are amino acids balanced?

A
  • Dietary protein
  • Endogenous protein
  • Synthesis of proteins
  • Synthesis of pyrimidines/purines/hormones etc..
  • Creating new carbon sources for gluconeogenesis
  • From carbon skeletons of dietary glucose
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2
Q

Which toxic sunstance is created when amino acids are broken down?

A

Ammonia

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3
Q

Ammonia is made into?

A

Urea

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4
Q

With what diet are amino acids especially mobilized?

A

Low carbohydrate diet

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5
Q

Which two amino acids are only ketogenic and to what metabolite are they converted to

A
  • Lysine
  • Leucine
  • Converted to Acetyl CoA
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6
Q

Which amino acids are preferably used in gluconeogenesis?

A
  • Alanine to pyruvate
  • Glutamine to alpha-ketoglutarate
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7
Q

Which two amino acids are converted into oxaloacetate and are only glucogenic

A
  • Aspartate
  • Asparagine
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8
Q

Which amino acid and keto acid can convert via transamination to alanine and alpha-ketoglutamine?

A

Glutamate and pyruvate

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9
Q
A
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10
Q

How is alpha-ketoglutarate converted to glutamine for transportation to the liver?

A
  1. alpha-ketoglutarate to glutamate via GDH (glutamate dehydrogenase)
  2. Glutamate to glutamine via glutarine synthase
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11
Q

How is glutamine converted to alpha-ketoglutarate again to release ammonia in the liver?

A
  1. Glutamine to glutamate via glutaminase
  2. Glutamate to alpha-ketoglutarate via glutamate dehydrogenase
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12
Q

Where does the urea cycle occur?

A

Liver only

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13
Q

A surplus of amino acids leads to the transamination into which metabolite?

A

Glutamate

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14
Q

How can glutamate be directly deaminated?

A

From glutamate to alpha-ketoglutarate by glutamate dehydrogenase

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15
Q

What is the first and rate-limiting step of the urea cycle?

A

Ammonia + bicarbonate + 2ATP to carbamoyl phosphate and 2ADP+phosphate

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16
Q

Via which amino acid does carbamoyl phosphate convert to arganine?

A

Aspartate

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17
Q

What is the last step from arganine to produce urea?

A

Arganine is cleaved by arginase

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18
Q

How is the urea cycle related to the citric acid cycle?

A

Aspartate in the urea cycle can enter the citric acid cycle to oxaloacetate

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19
Q

How does an increase in arginine influence the urea cycle?

A
  1. Arganine induces production of N-acetyl-glutamate from acetyl CoA and glutamate
  2. N-acetyl-glutamate induces the production of carbamoyl phosphate
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20
Q

What are the consequences of inborn errors in the urea cycle?

A

Hyperammonia which leads to death

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21
Q

Which two amino acids are taken away from the amino acid pool to treat hyperammonemia?

A
  • Glycine
  • Glutamine
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22
Q

What are the two excretion pathways of the liver

A
  • Hydrophobic via feces and bile
  • Water soluble via circulation and kidney
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23
Q

What determines effective concentration of a drug?

A

Drug half-life

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24
Q

Which enzymes in oxidation are strongly influenced by alcohol?

A

Cytochrome P450

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25
Q

Which energy compound does cytochrome P450 use?

A

NADPH

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26
Q

What are the two reaction phases of detoxification of vinyl chloride

A
  1. Chloroethylene oxide (Binding to proteins and DNA)
  2. Chloroacetaldehyde (Excreted by coupling to hydrophillic structures)
27
Q

What is glutathione?

A

Antioxidant: it removes xenobiotica

28
Q

What compound is needed in glutathione reduction and produced in the oxidative PPP?

A

NADPH

29
Q

What does glucuronate do?

A

A product that binds xenobiotica, drugs etc to produce glucoronides.

30
Q

What are glucoronides?

A

Substance made from glucose to bind to toxin that are secreted via feces/bile and the kidneys

31
Q

What are two ways to use glucose to detoxify the liver?

A
  • Glutathione (Kidney)
  • Glucuronate (Feces/bile)
32
Q

Describe the steps of toxic hemoglobin detoxification?

A
  1. Heme binds to bilirubin to form bilirubin-albumin
  2. bilirubin-albumin forms bilirubin diglucuronide by binding bilirubin to UDP-glucuronate
  3. Excreted into feces via bile
33
Q

What are the 4 ways for xenobiotics to be excreted from the kindeys?

A
  • Glucoronate
  • Glutathione
  • PAPS
  • Oxidation by cytochrome P450
34
Q

How can xenobiotica be excreted hydrohpobically?

A

Via bilirubin in bile

35
Q

What is the end product of metabolism of ethanol?

A

Acetate

36
Q

To which metabolite can acetate be converted to?

A

Acetyl CoA

37
Q

What is a characteristic of ALDH2’2 homozygotes

A

Never found in alcoholics

38
Q

What is the difference between the Km of ALDH2 and ALDH2’2

A

ALDH2’2 has a higher Km

39
Q

What is the result of a higher Km in aldehyde dehydrogenase?

A

The toxic effects of acetaldehyde are worse in people with ALDH2’2

40
Q

Is ALDH2’2 more common among caucasians or asians?

A

Asians

41
Q

How can acetate be used by tissues?

A

Acetate can be converted to acetyl CoA in the muscles, heart and even brain as a fuel source

42
Q

What are the four stages of alcohol-induced liver damage?

A
  1. Alcoholic fatty liver
  2. Alcoholic steathepatitis (Recovery possible)
  3. Fibrosis (Recovery possible, scar tissue remains)
  4. Cirrhosis (Irreversible)
43
Q

What is steatosis?

A

Fatty liver

44
Q

What compound does alcohol dehydrogenase generate?

A

NADH

45
Q

NADH produced from alcohol dehydrogenase inhibits what?

A

TCA cycle

46
Q

What does an increase of NADH from alcohol dehydrogenase cause?

A

Lactate increase and fatty acid production

47
Q

Why can triglycerides not be transported by VLDL during increase of ethanol?

A

Acetyldehyde binds and destroys tubulin

48
Q

What is alcohol induced hepatitis?

A

Inflammation of the liver

49
Q

How is alchohol induced hepatitis induced?

A

The formation of NADH inhibits oxidation of free radicals

50
Q

How does the liver form scar tissue after long term alcohol consumption?

A
  1. Acetaldehyde activates kupffer cells
  2. Kupffer cells stimulate stellate cells which make scar tissue with collagen
51
Q

High NADH leads to which two problems?

A
  • Lactoacedosis
  • Hypoglycemia (Gluconeogenesis is blocked by NADH)
52
Q

What happens when gluconeogenesis is blocked on an empty stomach when drinking?

A

Ketone bodies are produced from fatty acids, which causes ketoacidosis by D-beta-hydroxybutyrate forming

53
Q

What happens when lactate and keto acids build up during drinking on an empty stomach?

A

Ketoacidosis and lactate increase CO2 in the blood which can cause coma

54
Q

What problems can alcohol inflict on metabolism?

A
  • Acetate in the blood (As fuel source)
  • Ketoacidosis (Gluconeogenesis blocked)
  • Fatty liver
  • Hypoglycemia (Pyruvate to lactate due to NADH)
  • Lactate acedemia
  • Inhibition drug metabolism
55
Q

Which back up system is activated by chronic alcohol consumption?

A

MEOS

56
Q

What does MEOS do?

A

Converts ethanol to acetaldehyde and NADPH to NADP+

57
Q

Which protein (also functions in detoxification) is activated after chronic alcohol consumption?

A

P450 subtype CYP2E1

58
Q

What are the downsides of P450 subtype CYP2E1?

A

More damage due to faster accumulation of acetaldehyde

59
Q

When P450 is active, how does it convert aspirin or paracetemol?

A

To NAPQI

60
Q

What does NAPQI cause when P450 converts e.g. aspirin?

A

Liver necrosis

61
Q

What is gamma-carboxyglutamate involved in?

A

Blood coagulation

62
Q

Which vitamin supports gamma-carboxylation?

A

Vitamin K

63
Q

What effect do alcohol and liver failure have on blood coagulation?

A

Anti-coagulant effect which causes bleeding

Biochemistry (13 decks)

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