1.2.3 – Functions of the

liver OCR – A2 – Module 2

14/04/2023

1By Piril Erel

Wide Range of functions of the liver

Control of:

Blood glucose levels, amino acid levels, lipid levels

Synthesis of:

RBC in the fetus, bile, plasma proteins, cholesterol

Storage of:

Vitamins A, D and B12 , iron, glycogen

Detoxification of:

Alcohol and drugs

Breakdown of hormones

Destruction of RBCs14/04/2023

2By Piril Erel

Formation of Urea

Daily requirement is 40-60g of protein, but daily consumption is far more greater therefore, breakdown of amino acids are needed as accumulation leads to toxicity.

Two step process occurs in the liver before the amino acid component is excreted DEAMINATION

ORNITHINE CYCLE

14/04/2023

3By Piril Erel

Formation of Urea DEAMINATION:

Removal of NH3 group fro the amino acid with oxygen forming a keto acid (-RCOCOOH) and Ammonia (NH3)

Ammonia is highly toxic and very soluble therefore should not be allowed to accumulate in the blood circulation.

On removal of NH3 group energy is released.

THE ORNITHINE CYCLE:

Ammonia is converted into a less soluble and less toxic substance when combined with CO2 forming Urea.

Urea is further passed into the blood circulation and into the kidneys where it is filtered out of the blood circulation and is concentrated in the urine.

14/04/2023

4By Piril Erel

Detoxification

The liver detoxifies alcohol and drugs. Toxins can also be rendered harmless by oxidation, reduction, methylation or a combination with another molecule.

Liver cells contain many enzymes that enable rendering of toxic molecules less toxic form.

This includes catalase which converts H2O2 to oxygen and water

DETOXIFICATION OF ALCOHOL:

Alcohol is a CNS depressant; contains a lot of energy that can be used for respiration.

STEP 1: Ethanol Ethanol dehydrogenase Ethanal (occurs in the hepatocytes)

STEP 2: Ethanal Ethanal dehydrogenase Ethanoic acid

STEP 3: Ethanoic acid Ethanoate + CoA Acetyl CoA

The hydrogens release in the steps above are combined with NAD NADH

NAD is required to oxidise and breakdown fatty acids for use in respiration

14/04/2023

5By Piril Erel

Future Possible Complications

If the liver has to detoxify too much alcohol it has insufficient NAD to deal with the fatty acids.

These fatty acids are converted back to lipids and are stored in the hepatocytes, causing the liver to become enlarged

Causes a condition known as fatty liver alcohol-related hepatitis or cirrhosis.

14/04/2023

6By Piril Erel

Stretching Your Knowledge

Scenario:

Liver cells contain a large group of enzymes called the cytochrome P450 enzymes. These are responsible for the breakdown of some toxic molecules, such as cocaine and other drugs (recreational and medicinal). The P450s are most concentrated in the endoplasmic reticulum of liver cells. As a result of variation these enzymes can be more effective in some people than in others (Caucasian population compared to Afro-Caribean population)

Many drugs can be more effective in some people than in others and may also cause variable side effects

Task:

1. Suggest why the P450s are most concentrated in the endoplasmic reticulum?

2. Suggest why many medicinal drugs have different side effects in different people

3. Explain why the P450s are not identical in every person. 14/04/2023

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The P450s are proteins; these are manufactured by the ribosomes that are attached to the endoplasmic reticulum – they can be packaged in vesicles and transported to where they are needed

Each person may have slightly different enzymes (evolution). These may break the drugs down in a slightly different way producing different by-products (SEs)

Genetic variation means that different people will have different alleles – these will produce slightly different enzymes.

By Piril Erel

Questions:

1. Why must ammonia be converted to urea?

2. Explain why excess amino acids and alcohol should not be excreted?

3. Suggest why the liver cells have large number of mitochondria and ribosomes

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Ammonia is highly soluble and very toxic; urea is less soluble and less toxic

They contain valuable energy that can be converted to useable forms. Some amino acids can be converted into other amino acids

The mitochondria provide ATP (metabolic energy) for the active or energy-requiring processes, e.g. protein synthesis, mitosis, active transport, endo and exocytosis. The ribosomes manufacture the many enzymes that are needed in liver cells.

By Piril Erel