Metabolic functions of the liver Flashcards
What is the liver extremely important in maintaining?
extremely important for maintaining constant blood glucose levels
How does the liver maintain constant blood glucose level?
- By removal of glucose from the blood after a meal,
- By storing glucose in the form of glycogen,
- By restoring blood glucose levels through glycogenolysis and gluconeogenesis,
- By regulating the fluxes through glycolysis, gluconeogenesis and pentose phosphate cycle
What is the liver involved in the metabolism of?
involved in the metabolism of other sugars, such as fructose and galactose
What is the liver the major site of synthesis of?
liver is the major site for the synthesis of many serum proteins, such as albumin and the blood clotting factors.
What does the liver degrade, and particularly when?
liver degrades excess amino acids, particularly during gluconeogenesis
What is the liver the major site involving amino acids for?
The liver is the major site for transamination and deamination of amino acids, and for detoxification of ammonia.
What interaction is there between muscles and liver?
Gluconeogenesis in the liver allows the synthesis of glucose which can be transported to muscles when the muscle requires it
How much cholesterol is made by the liver?
- 50% of cholesterol made in the body is made by the liver
Where is the rest of cholesterol made by?
rest made by intestine, adrenal cortex and reproductive tissue
How is cholesterol synthesized in the liver and what enzymes are involved?
- Made from acetyl CoA and the key enzyme is HMG-CoA reductase
What is cholesterol transported as in the liver?
- Transported from the liver as VLDL
How is cholesterol excreted from the body?
- disposed of by the biliary system either as cholesterol or following conversion to bile acids/salts
How does cholesterol enter the livers cholesterol pool?
- Cholesterol enters the livers cholesterol pool from a number of sources
o dietary
o de novo by extra-hepatic tissue
o makes its own
What flux is not tightly regulated in humans?
- In humans the flux of cholesterol is not tightly regulated. With time there is an accumulation of cholesterol in the tissues particularly in the endothelial cells
What are the 2 routes of the metabolism of ethanol?
– Oxidation through the activity of alcohol dehydrogenase
– Microsomal oxidation using cytochrome P450
How much ethanol does the body approximately metabolize per hour?
- The body metabolises approximately 10g of alcohol/hour
What is methanol metabolised into?
- Methanol is metabolised to formaldehyde
Side effect of formaldehyde and why?
associated with paralysis, loss of consciousness and blindness because its toxic
What drugs can alcoholics be treated with?
- Alcoholics can be treated with drugs that inhibit ALDH thereby inducing the symptoms experienced
What is not a good negative inhibitor and therefore what will accumulate?
- NADH is not a good negative inhibitor of either ADH or ALDH therefore NADH generated in the cytosol will accumulate
What are 3 problems with the metabolism of ethanol?
- Oxidation of alcohol takes precedence over other nutrients
- The metabolism of alcohol is not regulated by negative feedback
- As a result, large quantities of acetyl-CoA, NADH, and ATP are formed
What pathways are inhibited by the metabolism of ethanol?
- acetyl-CoA, NADH and ATP are formed and they inhibit glucose metabolism by inhibiting PFK and pyruvate dehydrogenase
- NADH inhibits the TCA cycle and acetyl-CoA increases further
- acetyl-CoA results in ketone body formation and the stimulation of fatty acid synthesis
- Fatty acids are esterified to TG for export as VLDL
The steps and consequences due to high levels of NADH
- High levels of NADH inhibits fatty acid oxidation therefore FA accumulate in the liver.
- Increase G-3-P production together with the above leading to increased TG formation
- TG are incorporated into VLDL and released into the blood causing hyperlipidaemia.
- The high NADH/NAD ration shifts the OAA in the TCA cycle to malate and the acetyl-CoA formed from ethanol is diverted to ketone body formation leading to alcohol induced ketoacidosis
- The high NADH/NAD ration pushes the activity of lactate dehydrogenase towards lactate resulting in lactic acidosis
- The high NADH/NAD ration inhibits gluconeogenesis in a fasting individual this would lead to hypoglycaemia
What is the second route of metabolism of ethanol?
Microsomal Ethanol-Oxidising System (MESO)
