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Flashcards in GIS16 Functions Of The Liver Deck (9)
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1
Q

Carbohydrate metabolism in liver

A
  1. Fructokinase [liver]
    Fructose —> F-1-P —> DAP —> feed into glycolysis —> generate ATP anaerobically / aerobically (NADH)
  2. Galactokinase [liver]
    Galactose —> Gal-1-P —> G-1-P —> feed into glycolysis —> generate ATP anaerobically / aerobically (NADH)

Storage: polymer of Glucose rather than fructose / galactose —> Glycogen

2
Q

Amino acid metabolism

A

Fed state: Amino acids —>

  1. Proteins (e.g. albumins, cell proteins, muscle protein etc.)
  2. Nitrogen-containing compounds
    - glutathione
    - Creatine —> Creatine phosphate
    - monoamine neurotransmitter e.g. dopamine, noradrenaline, adrenaline, serotonin
  3. Glucose (Carbon skeleton of a.a.) —> glycogen / blood
  4. CO2

Fasting:
Muscle protein —> amino acids —> TCA cycle —>
1. **Glutamine —> **Gut / Kidney —> Alanine to liver / Deamination in kidney —> Serine / Alanine —> glucose / ketones bodes / urea
2. ***Alanine —> Liver —> glucose / ketones bodes / urea
3. Other a.a. —> Liver —> glucose / ketones bodes / urea

  • **Functions of liver:
    1. Produce Urea —> urine
    2. Produce Glucose
    3. Produce Ketone bodies

Ketone bodies: energy for muscle / kidney
Glucose: energy for brain / RBC

3
Q

Fate of amino group

A

**Liver cells mitochondria:
Transamination coupled to Oxidative Deamination
—> release NH2 (amino group) as **
ammonia
—> **Hyperammonemia: failure of liver to dispose excess ammonia from catabolism of N-containing compound
—> Ammonia into body cells + α-ketoglutarate —> Glutamate
—> α-ketoglutarate **
depleted
—> TCA cycle stopped (dangerous for tissue dependent on oxidative phosphorylation)

  1. Transamination:
    - **Alanine / Other a.a. —(減去NH2)—> **Pyruvate —> Glucose
    —> **α-ketoglutarate (獲得NH2) —> **Glutamate
  2. Subsequent Transamination:
    - Glutamate —(減去NH2)—> α-ketoglutarate
    —> **Oxaloacetate —(獲得NH2)—> **Aspartate
    —> **Aspartate
    —> **
    Urea cycle
    —> 第一個 amino group in urea

(Glutamate-oxaloacetate transaminase (GOT) / Aspartate aminotransferase (AAT))

  1. Oxidative Deamination:
    - **Glutamate dehydrogenase (GDH)
    —> Glutamate (減翻NH2) —> α-ketoglutarate (同一時間NAD —> NADH)
    —> NH4+ released as ammonia
    —> Urea cycle
    —> **
    Carbamoyl phosphate
    —> 第二個 amino group in urea

記住:

  • Glutamate配α-ketoglutarate
  • Aspartate配Oxaloacetate
4
Q

Sources of NH4

A
  1. Glutamine —> Glutamate
    * **2. Glutamate —> α-ketoglutarate (Oxidative deamination)
  2. Asparagine —> Aspartate
  3. Aspartate —> Fumarate (Purine nucleotide cycle)
  4. Urea
  5. Serine —> Pyruvate
  6. Threonine —> α-ketobutyrate
  7. Histidine —> Urocanate
5
Q

***Urea cycle

A

Urea: have 2 amino groups
First one: from **Carbamoyl phosphate
Second one: from **
Aspartate

Mitochondrion:
1. CO2 + NH4 —(**Carbamoyl phosphate synthetase 1, use ATP)—> **Carbamoyl phosphate (第一個NH2)

  1. captured by Ornithine (an amino acid):
    * **Ornithine —(Ornithine transcarbamoylase)—> Citrulline

Outside mitochondrion:
3. **Citrulline + **Aspartate (第二個NH2) —(Argininosuccinate synthetase, use ATP)—> Argininosuccinate

  1. Argininosuccinate —(Argininosuccinase)—> ***Arginine + Fumarate
  2. **Arginine + H2O —(Arginase: hydrolysis)—> **Urea + Ornithine
  3. Ornithine continue into cycle capturing NH2 group from Carbamoyl phosphate
6
Q

Feed-forward regulation of Carbamoyl phosphate formation

A

Arginine (from food) promote:
- Glutamate + Acetyl CoA —> N-Acetyl-glutamate

N-Acetyl-glutamate promote:
- Conversion of CO2 + NH4 —> Carbamoyl phosphate

Overall: Eat more protein rich food —> contain more Arginine —> force more ***Carbamoyl phosphate formation —> ↑ Urea cycle —> ↑ NH4 excretion

7
Q

Fatty acid metabolism

A
  1. ↑ Lipolysis (fasting, high fat/low carb diet, diabetes)
  2. ↑ Glucagon / insulin ratio
  3. ↑ Ketogenesis (in liver mitochondria: synthesis of ***Acetoacetate)
    - 2 x Acetyl CoA
    —> Acetoacetyl CoA —> (+ 1 Acetyl CoA by HMG CoA synthetase)
    —> HMG CoA —> (- 1 Acetyl CoA by HMG CoA lysase)
    —> Acetoacetate (Ketone bodies)
    —(spontaneous)—> Acetone

Other ketone bodies:

  • D-β-hydroxybutyrate
  • Acetone —> (reaching lung) —> acetone breath (in Ketosis: too many ketone bodies formed)
8
Q

Use / Oxidation of ketone bodies

A

Liver synthesise Acetoacetate
—> not yet converted to Acetoacetyl CoA
—> since Acetoacetate CoA transferase / ***Thiotransferase activity is low in liver mitochondria

Instead
—> transport to Muscle, Kidney, Brain mitochondria (where ***Thiotransferase activity is higher)
—> Acetoacetyl CoA (by Thiotransferase, CoA group from Succinyl CoA)
—> Acetyl-CoA
—> enters TCA cycle to generate energy

9
Q

Haem degradation

A
Haemoglobin
—> ***Heme (+ Globin) (Heme oxygenase)
—> ***Biliverdin
—> ***Bilirubin (+ Fe + CO) (in reticuloendothelial system of spleen)
—> Bilirubin-albumin

Bilirubin (放翻走albumin)
—> + UDP-Glucuronate (by UDP-glucuronosyl transferase in hepatocytes ER)
—> **Bilirubin diglucuronide (more water soluble)
—> Bile
—> **
Urobilinogen in urine / ***Stercobilin in faeces