Mammalian Physiology and Behaviour

THE LIVER

THE LIVER

ROLES OF THE LIVER

Carbohydrate Metaoblism

• (c) Explain the roles of the liver in carbohydrate metabolism and the production of glucose from amino acids.

• Interconversion of glucose and glycogen

• Conversion of other substances to glucose

Control of Glucose in blood

Glucose and Glycogen

• Glycogen is stored in the liver (25%) and the muscles (75%)

• Glucagon causes the breakdown of Glycogen to Glucose

• In the Hepatocytes• This is called Glycogenolysis

Glucose and Glycogen

• Adrenaline has similar effect to Glucagon

• Insulin gets Hepatocytes to convert Glucose to Glycogen

Conversion of Substances to Glucose

• Non-carbohydrates can be converted to glucose

• E.g. amino acids, fats, lactate and pyruvate

• Where do lactate and pyruvate come from?

• This is called GLUCONEOGENESIS• Occurs in very low blood sugar situations

when there is no more Glycogen

Lipid Metabolism

• (d) Explain the roles of the liver in fat metabolism, including the use of fats in respiration, the synthesis of triglycerides from excess carbohydrate and protein, the synthesis and regulation of cholesterol, and the transport of lipids to and from the liver as lipoproteins.

Fats for Energy

• Fats can be respired to produce ATP• Most tissues respire fats in

preference to glucose (especially cardiac muscle)

• Fats are split to fatty acids and glycerol

• Fatty acids are converted to acetyl coenzyme A

• This is used in the Krebs cycle

Synthesis of Triglycerides

• The liver converts unneeded carbohydrates and proteins to fats

• Fats are stored in adipose tissue• Why can’t fats be transported in

the blood?• They are insoluble• Transported as Lipoproteins

Lipoproteins

• Most fats are transported as Low Density Lipoproteins (LDLs)

• Hydrophobic lipids in the centre

• Polar lipids and proteins on the outside

Cholesterol combined with fatty acids

Synthesis of Cholesterol

• Cholesterol is made in the liver

• It has many useful functions in the body• Can you think of any?

Functions of Cholesterol

• Stability and fluidity of membranes• Synthesis of steroid hormones• Deposited in the skin for

waterproofing• Used to make Vitamin D• Used to make bile slats

Yet with all these uses how do wemost often hear about cholesterol?

Controlling Cholesterol

• It is present in the diet

• But when Cholesterol is absorbed in the intestines…

• The Liver will make less Cholesterol

Controlling Cholesterol

• Cholesterol presence reduces the activity of an enzyme that produces it from acetyl coenzyme A

• So dietary cholesterol doesn’t significantly affect blood cholesterol!

High Blood Cholesterol?

• It is saturated fats in the diet that can raise blood cholesterol

• This is because they increase the rate of production in the liver

Transport of Cholesterol

• Transported as:• Low Density Lipoproteins (LDLs)• Very Low Density Lipoproteins• High Density Lipoproteins (HDLs)• LDLs = Deposition of cholesterol on

blood vessel walls• HDLs = Protect against deposition

of cholesterol (may even remove it)

Protein Metabolism

(e) Explain the roles of the liver in deamination, transamination and urea formation

Deamination = Breakdown of excess amino acidsTransamination = Conversion of one amino acid to

another(apart from essential amino acids)

Deamination

• Urea is produced from excess amino acids • Getting rid of the whole amino acid would

be wasteful, so the Nitrogen is removed (NH2) group and the rest is kept

• The NH2 is combined with Hydrogen to form ammonia

• The organic acid can be turned into things like carbohydrates and fats

Animation of Deamination

Ornithine Cycle

• Ammonia is highly toxic and solubleConverted to

urea by combining with CO2

Via several amino acids

In Ornithine cycle

Requires energy

ATP

ATP

Synthesis of Plasma Proteins

• (g) Describe the production, and explain the roles, of the plasma proteins fibrinogen, globulins and albumin.

• All plasma proteins are soluble (globular)• They include:• Fibrinogen, Globulin and Albumin

• All made in the Liver

Plasma Proteins

• Fibrinogen and prothrombin are involved in blood clotting

• Albumin maintains the water level in the blood

• Globulin is most of the other globular proteins in blood plasma

Synoptic = link to tissue fluid formation!

Globulins

• Immunoglobulins are made by immune system not liver

• Others are made by liver and help in transporting substances

• e.g. thyroxine, insulin, phospholipids, lipids, cholesterol, iron, vitamins A/E/B12/D/K

Bile Formation

• Most of the cholesterol is used to make bile

• About 1000 cm3 per day• Made in hepatocytes• Secreted into bile canaliculi• To bile duct• Then to duodenum• Some will be stored in gall bladder

Bile composition

• Major components are water and bile salts

• Bile salts made from ___________• Emulsify fats• What effect does this have?• Easier digestion and absorption

Bile composition

• Bile also contains cholesterol itself• Precipitates out to form gall stones• If there is too much cholesterol or

too little bile salts

Breakdown of haemoglobin

• RBCs only last _________• Broken down in the spleen and liver• Haemoglobin is broken down into

Haem and Globin.• Globin broken down to amino acids• Heam broken down to Iron and

bilirubin

Breakdown of haemoglobin

• Iron stored in Liver• Bilirubin secreted into bile

• If bilirubin can’t be secreted into bile

• It stays in the blood• And causes jaundice

Alcohol

• What is the alcohol that is found in alcoholic drinks?

• Ethanol• How is it absorbed by the body?• Lipid soluble so can pass straight

through membranes

Alcohol

• Ethanol is toxic• Damages cells• Liver protects by breaking ethanol

down into harmless substances

Alcohol Metabolism

The Krebs Cycle

Excessive Alcohol Consumption

• Damages Liver cells• Metabolism of alcohol produces

reduced NAD• Stops oxidised NAD requiring

reactions• Including oxidation of fatty acids• Fatty acids are deposited in

hepatocytes• Reducing their efficiency

Cirrhosis

• Liver cells die• Replaced by fibrous tissue• Lobule structure is destroyed• Blood supply structure goes• Blood can flow straight through

without entering sinusoids• Lots of damaging effects because

Liver carries out so many functions