1. The Function of the Liver Objectives Describe the formation of urea in the liver, including an outline of the ornithine cycle. Describe the roles of the liver in detoxification.

2. What does the liver do? Synthesis and secretion Controls levels of…. Plasma proteins (inc clotting factors) Red blood cells (in foetus) Bile Glucose Cholesterol and lipoproteins Heat Lipid (storage in adipose) Glucose Amino acids Removal of…. Bilirubin (haem group from old RBC Used hormones e.g. sex hormones Detoxification of… Alcohol, Drugs, Ammonia Stores…. Glucose as glycogen Minerals Cu and Fe Key Vitamins A, D, E, K and B12 Saturated fat Immune system Macrophages called Kupfer cells

3. Role of Liver in digestion Produces bile that is stored in the gall bladder between meals and released into small intestines: Bile salts - emulsify fats Important for absorption of fat soluble vitamins from digested food (Vit. D,E,K & A) Neutralisation of excess acidity from stomach Bactericidal role (defence)

4. Formation of Urea XS aa in the diet cant be stored as the amine group makes them toxic so the aa is deaminated forming a keto acid and ammonia amino acidammonia + keto acid deamination The keto acid can enter respiration directly to release energy – gluconeogenesis

5. Formation of Urea Deamination forms ammonia which is highly toxic The ammonia enters the ornithine cycle to form less toxic, soluble urea for excretion by the kidneys amino acidammonia + keto acidurea deamination ornithine cycle

6. The ornithine Cycle

7. The ornithine cycle Ammonia combines with carbon dioxide to produce urea. Urea is reabsorbed back into 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

8. 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 ……..

9. Detoxification of Alcohol Ethanol (alcohol) depresses nerve activity. It contains energy so can be respired. It is broken down by hepatocytes to ethanal by the enzyme ethanol dehydrogenase. Ethanal dehydrogenase then breaks the ethanal down into ethanoate. Ethanoate combines with coenzyme A to form acetyl coenzyme A which can enter the respiratory pathway.

10. Detoxification of Alcohol The H + ions released during this process are used to reduce the coenzyme 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

11. Summary: 9 Basic Functions 1.Bile Synthesis – aids in fat digestion 2.Gluconeogenesis (when carbohydrate stores are depleted) 3.Storage of Fe, Cu and soluble vitamins (A,D,E,K) 4.Site of the ornithine cycle 5.Production of plasma proteins 6.Detoxification of poisons 7.Synthesis of cholesterol from acetyl co-A 8.Metabolism - amino acids, fats, carbohydrates 9.Phagocytosis of worn out red blood cells

12. Stretch and Challenge

13. What do other animals do? other mammals and amphibians make urea like us! Birds, reptiles and insects turn urea into uric acid and excrete it in faeces, but this uses LOTS of energy so WHY? Fish and aquatic invertebrates simply excrete their ammonia into the sea. Why is it OK?

14. Brown bears & Hibernation During winter, the brown bear, Ursus arctus, enters a long period of inactivity. During which it undergoes various physiological changes, such as a decrease in core body temperature and a decrease in resting heart rate. There are also changes in the brown bear’s metabolism of protein and lipids. During periods of inactivity, the brown bear reabsorbs all urea molecules from the filtrate in its kidneys and from the bladder. Urea is transported in the blood to the large intestine where Bacteria convert urea to ammonia and CO 2, which diffuse back into the blood. When the ammonia reaches the liver, it is converted into amino acids which are then used to synthesise proteins in the body, especially in the liver and muscle cells. Describe the similarities and differences between the metabolism of nitrogen-containing compounds in inactive brown bears, as described in the passage, and in humans.

15. Brown bears & Hibernation similarities 1production of urea ; 2urea transported in blood ; 3urea filtered from blood ; 4synthesis of proteins from amino acids differences (assume refs are to brown bears unless otherwise stated) 5amino acids synthesised from ammonia 6all urea reabsorbed ; 7from kidney and bladder ; 8urea converted to ammonia by bacteria 9AVP ; e.g. (humans) less tolerant to high ammonia (in blood)max 5 Describe the similarities and differences between the metabolism of nitrogen-containing compounds in inactive brown bears, as described in the passage, and in humans. This was a very good discriminator, as only the most able candidates were able to score the five marks available, despite the fact that much of the information had been presented to them in the preceding text. Weaker candidates failed to use this material, despite being directed to do so in the stem of the question. Instead they concentrated on their own knowledge of the metabolism of nitrogenous compounds in humans, giving details of deamination and the ornithine cycle, neither of which was relevant. Furthermore, some candidates neglected to put their responses under the appropriate headings of ‘similarities’ and ‘differences’, thereby losing marks for otherwise correct statements. Most candidates appreciated that humans and bears use amino acids in the synthesis of proteins and many stated that urea would be produced in both mammals. There were fewer references to either the transport of urea in the bloodstream or to the filtration of urea. With regard to the differences, a number of vague statements were seen, such as the conversion of urea to ammonia without mention of the role of bacteria in this process or precisely where reabsorption of urea would take place. Better candidates understood that amino acids could be synthesised from ammonia in bears although some believed that this would also take place in humans.