Metabolic functions of the liver Flashcards
How does liver maintain blood glucose levels?
- Removes glucose from the blood after a meal
- Stores glucose in the form of glycogen
- Restores blood glucose levels through glycogenolysis and gluconeogenesis
- Regulates fluxes through glycolysis, gluconeogenesis and pentose phosphate cycle
- Can convert glucose to fatty acids, which can later be converted back to glucose if need be
- Excess lactate in the muscle is converted to glucose in the liver through gluconeogenesis.
What is the role of the liver in protein and amino acid metabolism?
Liver is a major site for synthesis of many serum proteins e.g. albumin and blood clotting factors.
Body doesn’t store protein meaning excess protein is broken down, particularly during gluconeogensis:
- Glucogenic amino acids will be converted to sugars
- Ketogenic amino acids will be converted to ketone bodies
Liver is major site for transamination and deamination of amino acids and for the detoxification of ammonia through production of urea.
What is the role of the liver in fat transport?
Liver involved in:
- fatty acid synthesis
- transport
- Beta oxidation
Chylomicrons synthesised in the gut transport the triglycerides produced in the liver to peripheral tissues. Chylomicron remnants go back to the liver where there will be repackaging of lipids into lipoproteins.
What is the role of the liver in the synthesis and removal of cholesterol?
Liver synthesises cholesterol (50%) and removes cholesterol.
Cholesterol can’t be used for energy and body can’t degrade cholesterol so it is disposed of by the biliary system either as unmodified cholesterol or following conversion to bile acids/salts
Cholesterol enters liver’s cholesterol pool via:
- diet
- de novo by extra-hepatic tissue
- makes its own cholesterol.
What is the role of the liver in the metabolism of ethanol?
2 routes of ethanol metabolism:
-Oxidation through ALDH (90%-predominant route)
-Microsomal Ethanol Oxidising System (MEOS) using cytochrome P450 enzymes (10%)
What is the Microsomal ethanol oxidizing system (MEOS)?
A liver enzyme system that oxidizes ethanol to acetaldehyde by CYP450 enzymes
its activity predominates at higher levels of alcohol intake.
uses NADPH which is required for the synthesis of the antioxidant glutathione.
What is Acetylaldehyde?
Highly reactive and can accumulate with excessive ethanol intake.
Can inhibit enzyme function, leading to a reduction in secretion of both serum protein and VLDL
Enhances free radical formation, leading to tissue damage such as inflammation and necrosis.
What are the Three stages of alcoholic liver disease?
Stage 1: fatty liver
stage 2: alcohol hepatitis (groups of cells die resulting in inflammation)
stage 3: cirrhosis (includes fibrosis, scarring and cell death).
Explain the Liver cirrhosis effect.
Cirrhotic liver cannot function properly, ammonia will accumulate resulting in neurotoxicity, coma and death.
What are Xenobiotics?
substances that are foreign to a biological system:
- plant metabolites
- synthetic compounds
- food additives
- agrochemicals
- cosmetics
- by products of cooking
- drugs
Describe Liver and xenobiotic metabolism?
Aim is to make xenobiotic harmless and more readily disposed of by the kidney or the gut in faeces. Also involved are the intestines and lungs.
3 phases of xenobiotic metabolism:
- phase I: oxidation
- phase II:conjugation
- phase III: elimination..
What is the role of statins?
Regulate cholesterol metabolism and are used to treat high blood cholesterol by inhibiting HMG-CoA Reductase, the key regulatory enzyme in cholesterol synthesis.
What are statins degraded by?
Degraded by CYP3A4
CYP3A4 itself is inhibited by grapefruit juice, so if you consume grapefruit juice while taking statins, statin levels can rise by 15 fold (huge increase in dosage).
Explain Liver Metabolism of Aflatoxin B1.
Aflatoxin B1 is a poisonous carcinogen produced by the fungus Aspergillus flavus and found in peanuts
If Aflatoxin is metabolised by P450 enzymes it will lead to epoxide formation (which is extremely toxic and even worse than Aflatoxin) and hepatocarcinogenesis (liver tumour).
