OCR Specification focus:
‘Liver roles include glycogen storage, detoxification, and converting ammonia and carbon dioxide to urea via the ornithine cycle (detail not required).’
The liver plays a vital role in maintaining homeostasis by regulating blood composition, detoxifying harmful substances, storing nutrients, and excreting waste products through metabolic processes.
The Liver and Its Role in Homeostasis
The liver is a large metabolic organ located in the upper right of the abdomen. It acts as a central hub for chemical processing, ensuring internal conditions remain stable. It achieves this through metabolic regulation, detoxification, nutrient storage, and waste conversion, all of which contribute to maintaining homeostasis — the steady internal environment essential for optimal cellular function.
Importance of Liver Functions
The liver’s activities maintain:
Stable blood glucose levels via glycogen storage and mobilisation.
Safe blood composition by detoxifying harmful compounds.
Nitrogen balance through the conversion of ammonia to urea.
Balanced plasma protein levels by synthesising albumin and clotting factors.
Disruption in liver function can lead to serious physiological imbalances, such as hypoglycaemia, toxin accumulation, or hyperammonaemia.
Glycogen Storage and Blood Glucose Regulation
A major homeostatic role of the liver is regulation of blood glucose concentration. It acts as a glucose buffer, storing and releasing glucose as needed to maintain balance.
Diagram of negative feedback control of blood glucose, showing insulin-stimulated glycogenesis (glucose → glycogen) and glucagon-stimulated glycogenolysis (glycogen → glucose) in the liver. Arrows indicate when each hormone predominates. The diagram focuses on the feedback loop and the liver’s buffering function without unnecessary pathway detail. Source.
Glycogenesis and Glycogenolysis
Glycogenesis occurs when blood glucose levels are high:
Glucose is converted into glycogen for storage under the influence of insulin.
Glycogenolysis occurs when blood glucose levels fall:
Glycogen is broken down to release glucose under the influence of glucagon and adrenaline.
Homeostasis: The maintenance of a constant internal environment despite external changes.
The liver’s ability to alternate between glycogenesis and glycogenolysis enables rapid adjustments to blood glucose, ensuring a consistent supply to organs such as the brain and muscles.
Gluconeogenesis
When glycogen reserves are depleted, the liver synthesises glucose from non-carbohydrate sources like amino acids and glycerol. This process, gluconeogenesis, prevents hypoglycaemia during prolonged fasting or intense exercise.
Detoxification of Harmful Substances
The liver performs detoxification, converting potentially harmful chemicals into less toxic or excretable forms.
Breakdown of Alcohol and Drugs
The enzyme alcohol dehydrogenase in hepatocytes converts ethanol to ethanal (acetaldehyde), and subsequently to ethanoic acid (acetate).
Simplified pathway of ethanol detoxification: ADH converts ethanol to acetaldehyde, then ALDH converts acetaldehyde to acetate, which becomes CO₂ and H₂O. This captures the main hepatic route; the page also mentions CYP2E1 and catalase, which are ancillary pathways beyond the OCR core requirement. Labels are concise and appropriate for A-level students. Source.
Acetate is then used in respiration or converted into fat for storage.
Many drugs, such as paracetamol, are metabolised in the liver to render them harmless.
Excessive alcohol consumption damages hepatocytes, leading to fatty liver, hepatitis, or cirrhosis — conditions that impair homeostatic regulation.
Removal of Hormones and Toxins
The liver inactivates steroid hormones and insulin, preventing overstimulation of target tissues.
It also removes ammonia, a highly toxic by-product of amino acid metabolism, through conversion into urea.
Detoxification: The metabolic process by which toxic substances are converted into less harmful or excretable forms by the liver.
Conversion of Ammonia to Urea: The Ornithine Cycle
Proteins cannot be stored, so excess amino acids are deaminated in the liver. The amine group (-NH₂) is removed, forming ammonia (NH₃), which is toxic. The liver converts this ammonia to urea, a far less toxic compound, via the ornithine cycle.
Schematic of the urea (ornithine) cycle showing the transformation of ammonia and carbon dioxide into urea in hepatocytes. Key intermediates (ornithine, citrulline, argininosuccinate, arginine) and enzymes (CPS-I, OTC, ASS, ASL, ARG1) are labelled. This image includes enzyme names and intermediates beyond OCR’s required detail but clarifies the overall flow. Source.
Although OCR students are not required to know the detailed steps of the cycle, understanding its purpose is essential:
Ammonia and carbon dioxide are combined in a sequence of reactions involving the amino acid ornithine.
The resulting urea is released into the bloodstream and excreted by the kidneys.
This conversion is crucial in maintaining nitrogen homeostasis and preventing ammonia toxicity.
Overview of Related Processes
Deamination: Removal of amino groups from amino acids to produce ammonia.
Transamination: Transfer of amino groups between amino acids, aiding amino acid synthesis.
Urea formation: Conversion of ammonia and CO₂ to urea.
Deamination: The removal of an amino group from an amino acid, forming ammonia and an organic acid.
The Liver’s Role in Metabolic Regulation
Beyond glucose and nitrogen metabolism, the liver regulates various other biochemical pathways contributing to homeostasis.
Lipid Metabolism
Converts excess carbohydrates and proteins into fatty acids and triglycerides for storage.
Oxidises fatty acids for energy when glucose is scarce.
Synthesises cholesterol and phospholipids for cell membranes.
Protein and Plasma Component Synthesis
The liver produces essential plasma proteins, such as:
Albumin, which maintains osmotic balance and blood volume.
Fibrinogen and prothrombin, vital for blood clotting.
Globulins, which serve immune and transport roles.
Osmotic balance: The equilibrium between water and solute concentrations across membranes, maintaining proper hydration of cells and tissues.
Vitamin and Mineral Storage
The liver stores:
Vitamin A, vital for vision and immune function.
Vitamin D, important for calcium regulation.
Vitamin B12, essential for red blood cell formation.
Iron, stored as ferritin, and copper, both crucial for haemoglobin synthesis.
These reserves ensure continuous supply during dietary fluctuations, supporting metabolic stability.
Summary of Key Homeostatic Contributions
The liver supports homeostasis through:
Carbohydrate regulation: Glycogen storage and glucose release.
Protein metabolism: Deamination and urea formation.
Lipid management: Fat synthesis and breakdown.
Detoxification: Breakdown of toxins, drugs, and hormones.
Synthesis and storage: Plasma proteins, vitamins, and minerals.
By integrating these processes, the liver sustains the chemical equilibrium of the blood and enables the body to adapt dynamically to metabolic changes.
FAQ
The liver regulates amino acid levels through transamination, where an amino group is transferred from one amino acid to a keto acid to form another amino acid.
This allows the liver to synthesise non-essential amino acids when dietary intake is low. Excess amino acids are deaminated, and their carbon skeletons can be converted into glucose or lipids depending on energy requirements.
Through these processes, the liver prevents amino acid deficiency or accumulation, helping to maintain nitrogen and energy balance.
The liver receives blood from two sources:
The hepatic artery, which supplies oxygenated blood from the heart.
The hepatic portal vein, which brings nutrient-rich blood from the digestive system.
This dual supply ensures the liver can process absorbed nutrients immediately and maintain sufficient oxygen for high metabolic activity.
It allows rapid detoxification and energy regulation before blood circulates to the rest of the body.
Hepatocytes have a large number of mitochondria, reflecting their high metabolic activity. They also contain extensive smooth and rough endoplasmic reticulum for enzyme production, detoxification, and protein synthesis.
Their arrangement in hepatic lobules, with close contact to blood sinusoids, ensures efficient exchange of substances between blood and liver tissue.
This structural adaptation allows hepatocytes to perform simultaneous functions such as glycogen storage, protein synthesis, and detoxification efficiently.
Once harmful compounds are converted into less toxic forms, the products follow different routes:
Water-soluble substances, such as urea or some drug metabolites, are released into the bloodstream and excreted by the kidneys.
Lipid-soluble substances may be incorporated into bile and excreted via the intestines.
Some metabolites, like acetate from alcohol breakdown, are reused in respiration or fat synthesis. This ensures minimal waste and efficient resource use.
The liver helps maintain blood pH by controlling the concentration of acidic and basic compounds.
It metabolises lactic acid from anaerobic respiration into glucose (Cori cycle).
It produces plasma proteins such as albumin, which act as buffers to stabilise pH.
During amino acid metabolism, it prevents excess production of acidic ammonia by converting it to urea.
These actions collectively prevent dangerous pH fluctuations that could disrupt enzyme activity and metabolism.
Practice Questions
Question 1 (2 marks)
Explain why the conversion of ammonia to urea in the liver is important for homeostasis.
Mark scheme:
1 mark for stating that ammonia is toxic and must be removed from the body.
1 mark for stating that conversion to urea makes it less toxic and easier to excrete in urine by the kidneys.
Question 2 (5 marks)
Describe the role of the liver in regulating blood glucose concentration and detoxifying harmful substances.
Mark scheme:
1 mark for stating that the liver stores glucose as glycogen when blood glucose levels are high (glycogenesis).
1 mark for stating that it breaks down glycogen to release glucose when blood glucose levels fall (glycogenolysis).
1 mark for mentioning the hormonal control of these processes by insulin and glucagon.
1 mark for explaining that detoxification occurs through enzymatic breakdown of harmful substances, such as alcohol by alcohol dehydrogenase.
1 mark for describing that the liver converts toxic ammonia into urea, which is then excreted by the kidneys, maintaining chemical balance in the body.
