Liver functions Flashcards
What does the liver synthesize? Give examples
Plasma proteins eg, albumin, globulin, fibrinogen
Clotting factors
Complement factors
Why is albumin important?
Maintenance of colloid osmotic pressure (could cause odema)
Binding and transport of large, hydrophobic compounds
Bilirubin, fatty acids, hormones, drugs
Antioxidant (traps free radicals)
Anticoagulant and antithrombotic effects
Why are globulins important?
- Make antibodies (not all are made by liver)
- Blood transport of: Lipids, (by lipoproteins), Iron, (by transferrin), Copper(by caeruloplasmin)
How is the liver involved in clotting?
- The liver produces all clotting factors (except: Calcium (IV), von Willebrand factor (VIII))
- Also Production of bile salts these are necessary for intestinal absorption of vitamin K (required to produce numerous clotting factors)
What are complement factors used for?
Important part of the immune response to pathogens
What is the liver’s role in protein metabolism – turnover and degradation, what causes an increase?
What are the two primary methods?
Continuous degradation and re-synthesis of all cellular proteins
70-80% of liberated amino acids are re-utilised into proteins
Variable rate – reflecting usage and demand
Increase seen in:
Damaged tissue due to trauma
Skeletal tissue during starvation – gluconeogenesis
2 primary methods:
- Lysosomal pathway
- Ubiquitin-proteosome pathway
What is the liver’s role in amino acid breakdown – turnover and degradation, what causes an increase?
What are the two primary processes?
Amino acid breakdown - When there is a surplus of amino acids = Degradation
Amino acid catabolism = Requires removal of alpha-amino group
Produces: Nitrogen (which is incorporated into other compounds or Excreted) and Carbon skeleton (which is metabolised)
The majority released as ammonia
2 processes of amino acid breakdown
- Transamination
- Oxidative deamination
Describe the process of transamination
This is a readily reversible process
Amino acid degradation (after protein-rich meal)
Amino acid synthesis (dietary supply ≠ cellular demand)
Transamination is the transfer of alpha-amino group from amino acid to alpha-ketoglutarate
Formation
- An alpha-keto acid (e.g. pyruvate) – Krebs’
- Glutamate is oxidative deamination and an amino group donor (synthesis of non-essential amino acids)
- Catalyst - Aminotransferase enzymes
Describe the process of oxidative deamination
Oxidative deamination is amino acid breakdown that results in the liberation of amino group as free ammonia
- Formation
An alpha-keto acid (e.g. pyruvate) (Krebs’)
Ammonia (Urea cycle) - Catalyst - Glutamate dehydrogenase and Co-enzymes (NAD+/NADPH)
It is a readily reversible process that is dependent upon relative concentrations of:
Glutamate, alpha-ketoglutarate, ammonia
After protein rich-meal, glutamate concentration is high
Reaction degrades amino acid glutamate → ammonia formation
What is nitrogen balance?
Nitrogen balance is a measure of the equilibrium of protein turnover;
Anabolic – positive balance
Catabolic – negative balance
(babies and pregnant women need more nitrogen per kg body mass than average adult)
Glucose/Alanine Cycle
Excess amino acids are metabolised. They are not stored for use as potential energy as this can be done more efficiently by other sources.
It produces α-keto acid which is fed into the Krebs cycle to be incorporated into glucose production and ammonia which is mainly excreted
Input of amine groups (NH2) comes from;
Dietary amino acids (9 cannot be synthesized by the human
body)
Alanine and glutamine from muscles
Describe the urea cycle
Removal of arginine due to diet or protein breakdown = produces urea which is excreted
One turn of the cycle consumes;
3 ATP equivalents
4 high energy nucleotides
Deficiencies in any of the enzymes involved is associated with higher levels of ammonia in the blood (mainly found in in mitochondria and cytosol) - absence of the enzymes is not compatible with life
What can occur due to high levels of ammonia
High levels of ammonia (neurotoxicity)
Increased ammonia crosses the BBB readily where it is
- Converted to glutamate (glutamate dehydrogenase)
- Decrease in α-ketoglutarate in brain
- Decrease in oxaloacetate
Krebs cycle stops
This leads to irreparable cell damage and neural cell death
What are absorptive and post-absorptive states of glucose regulation by the liver
- Absorptive state
Ingested nutrients are absorbed from the GI tract into the blood
A proportion of nutrients are catabolised and used
The remainder are converted and stored for future use - Post-absorptive state
Nutrients are no longer absorbed from the GI tract
Nutrient stores must supply the energy requirements of the body
How is glucose released in post-absorptive stage?
What is the synthesis of glucose called?
Glucose is no longer being absorbed from the GI tract
- Essential to maintain the plasma glucose concentration
- Almost always fuels the CNS (except in prolonged starvation)
Sources of blood glucose
- Glycogenolysis (hrs) = Hydrolysis of glycogen stores in liver (and skeletal muscle - forms glucose 6-phosphate in muscle, this undergoes glycolysis)
- Lipolysis = Glycerol released is enzymatically converted to glucose in the liver
- Proteolysis (>hrs) = Amino acids taken up by the liver and converted to glucose
The synthesis of glucose from above precursors (glycerol, amino acids) = gluconeogenesis
