5.2.3 The Mammalian Liver: Function

• The liver is mainly made up of cells known as hepatocytes that carry out almost all the functions required
• These functions include:
  • The storage of glycogen
  • The formation of urea
  • Detoxification

The storage of glycogen

• One of the main functions of the liver is to store glucose as the polysaccharide glycogen
  • The liver plays a vital role in the conversion of glucose into glycogen (a process known as glycogenesis)
  • The conversion between these molecules helps to regulate blood glucose concentration

• Glycogenesis is the synthesis of glycogen from glucose molecules
• Insulin triggers this process after it detects an increased blood glucose concentration
• The synthesis of glycogen removes glucose molecules from the bloodstream and decreases the blood glucose concentration to within a normal range
• Glycogen acts as a compact and efficient carbohydrate storage molecule

The formation of urea

• The protein in our diets is digested into amino acids
  • These amino acids are then absorbed into the blood and transported to the liver

• Instead of being excreted, excess amino acids (which are a good source of energy) are deaminated - the amino (-NH₂) group is removed so that the rest of the molecule can be used
• This process is known as deamination:
  • The amino group (-NH₂) of an amino acid is removed, together with an extra hydrogen atom
  • These combine to form ammonia (NH₃), which forms ammonium ions (NH₄⁺) in the cytoplasm
  • The remaining keto acid (a type of organic acid) may enter the Krebs cycle (in the mitochondria) to be respired, be converted to glucose, or converted to glycogen or fat for storage

Deamination of an amino acid

• Ammonia is a very soluble and highly toxic compound that is produced during deamination
• It can be very damaging if allowed to build up in the blood
• This is avoided by converting ammonia to urea
  • Urea is less soluble and less toxic than ammonia

• Ammonia is combined with carbon dioxide to form urea
• This occurs via a series of reactions that occur in a cycle, known as the ornithine cycle (or urea cycle)
  • During this cycle, one molecule of urea is produced from one molecule of carbon dioxide and two amino groups (from two amino acids)

• The urea diffuses through the phospholipid bilayer of the membranes of the hepatocytes and is then transported to the kidneys dissolved in the blood plasma

Formation of urea

Detoxification

• Detoxification is the term used to describe the breakdown (by the liver) of substances that are not needed or are toxic
• These substances include:
  • Lactate
  • Alcohol
  • Hormones
  • Medicinal drugs

Lactate metabolism

• Lactate is the end product of anaerobic respiration (produced by skeletal muscles during strenuous activity when there is insufficient oxygen in the blood - lactate diffuses out of the muscles and into the blood)
• Lactate is an energy-rich compound that can be respired by cardiac muscle and some other tissues. Excess lactate is absorbed by hepatocytes and metabolised
• In the liver, lactate is converted to pyruvate
  • Some of this pyruvate enters mitochondria and is respired aerobically to provide the energy required to convert the rest of the lactate to glucose
  • Some of this glucose is stored as glycogen and the remaining glucose enters the blood to maintain the blood glucose concentration 

Alcohol metabolism

• Once consumed, alcohol (in the form of ethanol) is absorbed in the stomach and transported in the blood until it is absorbed by hepatocytes
• Similar to lactate, ethanol is a source of energy that is respired by hepatocytes (in preference to fat)
  • The enzyme alcohol dehydrogenase converts ethanol into a molecule called ethanal, which is then converted into other molecules that enter respiration
• As the metabolism of ethanol generates a large amount of ATP, hepatocytes do not metabolise as much fat as usual and instead store the fat, which causes the condition known as fatty liver
• This stored fat reduces the ability of the hepatocytes to carry out their many functions and can eventually lead to severe problems such as cirrhosis, which is the scarring (fibrosis) of the liver caused by excessive alcohol consumption

Hormone metabolism

• Hormones are also metabolised
• Protein hormones (e.g. insulin and glucagon) and peptide hormones (e.g. anti-diuretic hormone) are hydrolysed into amino acids, which can then be converted to urea