Objectives: Describe the formation of urea in the liver, including an outline of the ornithine cycle. Describe the roles of the liver in detoxification. Functions of the Liver: Control of: blood glucose levels, amino acid levels, lipid levels. Synthesis of: red blood cells in the foetus, bile, plasma proteins, cholesterol Storage of: Vitamin A, D, B 12, iron, glycogen Detoxification of: alcohol, drugs Breakdown of hormones Destruction of red blood cells

Formation of Urea Excess amino acids in the diet cannot be stored as the amine group makes them toxic. The amino acid undergoes deamination (removal of the amine group) to form a keto acid and ammonia. The ammonia then enters the ornithine cycle to form the less toxic urea for excretion. amino acidammonia + keto acidurea deamination ornithine cycle

Deamination Produces ammonia which is highly toxic and very soluble, so it must not be allowed to accumulate. It also produces a keto acid which can enter respiration directly to release energy. H CCOOHNH 2 R + O2O2 R O COOHC + NH 3

The ornithine cycle The ammonia is combined with carbon dioxide to produce urea. Urea is less soluble and less toxic than ammonia. It can be passed back to the blood and transported to the kidneys where it is filtered into the urine. Urine is stored in the bladder until it is released from the body. 2NH 3 + CO 2 CO(NH 2 ) 2 + H 2 O

Detoxification Toxins may be produced by our body (e.g. hydrogen peroxide), may be taken in via our diet (e.g. alcohol), or may be consumed recreationally/medicinally (e.g. drugs). Toxins can be oxidised, reduced, methylated or combined with another molecule to make them harmless. Liver cells contain many enzymes that make toxins less toxic e.g. catalase breaks down hydrogen peroxide into? Can you remember from AS?

Detoxification of Alcohol Ethanol (alcohol) depresses nerve activity. It contains energy so can be used for respiration. It is broken down by hepatocytes by the enzyme ethanol dehydrogenase to ethanal. Ethanal dehydrogenase then breaks the ethanal down into ethanoate. Ethanoate combines with coenzyme A to form acetyl coenzyme A, and this molecule can enter the respiratory pathway. The hydrogen ions released during this process are used to reduce another coenzyme called NAD to form reduced NAD. NAD is also used in respiration to break down fatty acids. If the liver has to detoxify too much alcohol it has insufficient NAD to deal with the fatty acids and so these are converted back to lipids to be stored in the liver. This leads to the “fatty liver” condition and can lead to hepatitis or cirrhosis. Reduced NAD EthanolEthanalEthanoic AcidAcetyl Coenzyme A NAD To respiration