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
What is gluconeogenesis?
Gluconeogenesis is the process of generating new molecules of glucose from non-
carbohydrate precursors
Substrates = mostly pyruvate (formed from lactate and other amino acids) or glycerol (formed through triglyceride hydrolysis)
6 ATP molecules are consumed per molecule of glucose formed
What does the liver store?
Iron
Fat soluble vitamins (KADE)
Glycogen
Minerals
What is iron utilised and stored? How and where is it absorbed in the gut?
Distribution
Utilised by: Haemoglobin, Myoglobin, Bone marrow
Stored in: Liver, Reticulo-endothelial macrophages
Absorption:
1. Transferrin - Transports iron in the plasma to the bone marrow – iron incorporated into new RBC
- Ferritin- Storage form of iron, main source is found in the liver
Mostly absorbed in the duodenum
How are each of the fat soluble vitamins stored?
KADE
K - Necessary for production of clotting factors
A -Stored in Ito cells (in space of Disse), High levels stored in liver – prevent deficiency for 10 months
Function - Vision (retinal pigments), Healthy skin, Growth and reproduction
D- Liver storage prevents deficiency for 3-4 months, Function - Increases calcium reabsorption from intestinal tract, Promotes intestinal phosphate reabsorption
E- antioxidant
B12 - Liver stores prevent deficiency for >1yr
Promotes growth and RBC formation + maturation
Intrinsic factor (aids absorption - parietal cells of stomach)
absorbed in terminal ileum
How is glycogen stored? What is its purpose?
Sites of storage - Liver (~10% mass of liver) and Skeletal muscle (~2% mass of skeletal muscle) (overall storage of glycogen is greatest in muscle as mass is greater)
Glycogen is a readily mobilised storage form of glucose- Maintains blood glucose levels (lipids are primary source)
What minerals does the liver store?
Iron - Stored as ferritin
Copper
Describe fat metabolism
How is most of the body’s fat stored?
Blood glucose - 40- A few minutes
Glycogen - 600- Day
Muscle- 25,000 - 7-10 days
Lipid reserve- 100,000 - 30-40 days
Most of the body’s fat is stored in adipocytes which form tissues called adipose tissue. Some is stored in hepatocytes.
Describe the structure of triglycerides
Triglycerides (TGs, TAGs) consist of 3 fatty acids bound to a glycerol molecule.
It accounts for 78% of energy stored in body – proteins (21%) and
carbohydrates (1%).
Describe the different types of lipoprotein, where are they formed? What is the function?
Lipoproteins
HDL – formed in the liver
LDL – formed in plasma
VLDL – synthesized in hepatocytes
Also IDL.
They are used to transport cholesterol
through the blood.
What are lipids, what is their function?
Lipids are esters of fatty acids and certain alcohol compounds.
They have several functions;
- Energy reserves
- Structural – part of cell membrane
- Hormone metabolism
Describe the digestion and absorption of fats
- Bile salts and phospholipids emulsify dietary fats in the small intestine forming mixed micelles
- Intestinal lipases degrade TGs
- Fatty acids and other breakdown products are taken up into intestinal
mucosa and converted into triacyglycerols - Triacyglycerols are incorporated with cholesterol and apolipoproyeins
into chylomicrons - Chylomicrons move through the lymphatic system and bloodstream into the tissues
- Lipoprotein lipase converts triacyglycerols to fatty acids and glycerol
- Fatty acids enter cells
Fatty acids are oxidised as fuel or re-esterified for storage
What is fat catabolism, describe the process
Fat Catabolism – breaking down into smaller units
- Molecule of coenzyme A links to carboxyl at the end of a fatty acid
Breakdown of ATP > AMP + 2Pi
- Coenzyme A derivative of fatty acid proceeds through beta-oxidation reactions
- Molecule of acetyl coenzyme A is split off from fatty acid and 2H+ transferred to coenzymes
- Hydrogen atoms from coenzymes enter the oxidative phosphorylation
pathway to form ATP - Another coenzyme A attaches to fatty acid and the cycle is repeated
- Coenzyme – 2H molecules lead to the production of CO2 and ATP via the Krebs cycle and oxidative phosphorylation
Hepatic metabolism of lipids - lipoprotein lipase and hepatic lipase
Lipoprotein lipase
- Hydrolyses TGs in lipoproteins (chylomicrons, VLDLs) into 2 free fatty
acids and 1 glycerol molecule
Hepatic lipase
- Expressed in the liver and adrenal glands, it converts IDL into LDL
