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Biochemistry > Liver detoxification and alcohol > Flashcards

Liver detoxification and alcohol Flashcards

(63 cards)

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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
Which energy compound does cytochrome P450 use?
NADPH
26
What are the two reaction phases of detoxification of vinyl chloride
1. Chloroethylene oxide (Binding to proteins and DNA) 2. Chloroacetaldehyde (Excreted by coupling to hydrophillic structures)
27
What is glutathione?
Antioxidant: it removes xenobiotica
28
What compound is needed in glutathione reduction and produced in the oxidative PPP?
NADPH
29
What does glucuronate do?
A product that binds xenobiotica, drugs etc to produce glucoronides.
30
What are glucoronides?
Substance made from glucose to bind to toxin that are secreted via feces/bile and the kidneys
31
What are two ways to use glucose to detoxify the liver?
* Glutathione (Kidney) * Glucuronate (Feces/bile)
32
Describe the steps of toxic hemoglobin detoxification?
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
What are the 4 ways for xenobiotics to be excreted from the kindeys?
* Glucoronate * Glutathione * PAPS * Oxidation by cytochrome P450
34
How can xenobiotica be excreted hydrohpobically?
Via bilirubin in bile
35
What is the end product of metabolism of ethanol?
Acetate
36
To which metabolite can acetate be converted to?
Acetyl CoA
37
What is a characteristic of ALDH2'2 homozygotes
Never found in alcoholics
38
What is the difference between the Km of ALDH2 and ALDH2'2
ALDH2'2 has a higher Km
39
What is the result of a higher Km in aldehyde dehydrogenase?
The toxic effects of acetaldehyde are worse in people with ALDH2'2
40
Is ALDH2'2 more common among caucasians or asians?
Asians
41
How can acetate be used by tissues?
Acetate can be converted to acetyl CoA in the muscles, heart and even brain as a fuel source
42
What are the four stages of alcohol-induced liver damage?
1. Alcoholic fatty liver 2. Alcoholic steathepatitis (Recovery possible) 3. Fibrosis (Recovery possible, scar tissue remains) 4. Cirrhosis (Irreversible)
43
What is steatosis?
Fatty liver
44
What compound does alcohol dehydrogenase generate?
NADH
45
NADH produced from alcohol dehydrogenase inhibits what?
TCA cycle
46
What does an increase of NADH from alcohol dehydrogenase cause?
Lactate increase and fatty acid production
47
Why can triglycerides not be transported by VLDL during increase of ethanol?
Acetyldehyde binds and destroys tubulin
48
What is alcohol induced hepatitis?
Inflammation of the liver
49
How is alchohol induced hepatitis induced?
The formation of NADH inhibits oxidation of free radicals
50
How does the liver form scar tissue after long term alcohol consumption?
1. Acetaldehyde activates kupffer cells 2. Kupffer cells stimulate stellate cells which make scar tissue with collagen
51
High NADH leads to which two problems?
* Lactoacedosis * Hypoglycemia (Gluconeogenesis is blocked by NADH)
52
What happens when gluconeogenesis is blocked on an empty stomach when drinking?
Ketone bodies are produced from fatty acids, which causes ketoacidosis by D-beta-hydroxybutyrate forming
53
What happens when lactate and keto acids build up during drinking on an empty stomach?
Ketoacidosis and lactate increase CO2 in the blood which can cause coma
54
What problems can alcohol inflict on metabolism?
* 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
Which back up system is activated by chronic alcohol consumption?
MEOS
56
What does MEOS do?
Converts ethanol to acetaldehyde and NADPH to NADP+
57
Which protein (also functions in detoxification) is activated after chronic alcohol consumption?
P450 subtype CYP2E1
58
What are the downsides of P450 subtype CYP2E1?
More damage due to faster accumulation of acetaldehyde
59
When P450 is active, how does it convert aspirin or paracetemol?
To NAPQI
60
What does NAPQI cause when P450 converts e.g. aspirin?
Liver necrosis
61
What is gamma-carboxyglutamate involved in?
Blood coagulation
62
Which vitamin supports gamma-carboxylation?
Vitamin K
63
What effect do alcohol and liver failure have on blood coagulation?
Anti-coagulant effect which causes bleeding

Biochemistry (13 decks)

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