Biochemical aspects of liver metabolism Flashcards
What is the livers principle roles?
Final destination of absorbed products from the liver Bile production Elimination of unwanted molecules Secretion of plasma proteins Storage of important molecules Regulation of metabolism
Describe the plasma proteins?
Albumin
Alpha globulins
Beta globulins
Gamma globulins (immunoglobulins)
What allows separation of proteins by size - plasma proteins?
Electrophoresis
What are the main functions of plasma proteins?
Maintenance of oncotic or colloid osmotic pressure Transport of hydrophobic substances pH buffering Enzymatic Immunity
What is the function of alpha goblin?
Transports lipids, bilirubin, lipoproteins and some dietary metals
Retinol binding protein - transports Vitamin A
What is the function of beta globulins?
Transferrin - transports Fe3+, indicator of iron deficiency
Fibrinogen - inactive form of fibrin, clotting of the blood
What does transferrin do?
Transports Fe3+ - indicator of iron deficiency
What does fibrinogen do?
Inactive form of fibrin
Clotting of the blood
Describe albumin?
Most abundant plasma protein - main determinant of plasma oncotic pressure
What stimulates the production of albumin?
Insulin stimulates the production of albumin
What causes a decrease of albumin levels?
Starvation/low protein diet
What does albumin transport?
Endogenous lipophilic substances
Fatty acids
Bilirubin
Thyroid hormones
Exogenous
Drugs like aspirin
What is bilirubin the breakdown product of?
Breakdown product of haem
What is iron transported as?
Ferric iron Fe3+
What is Ferric iron Fe3+ bound to when being transported?
Transferrin
Where is iron stored?
In cells bound to ferritin
What is copper bound to when transported in the blood?
Ceruoplasmin
What is copper essential for?
The regulation of redox reactions, transport and use of iron
What is a deficiency of copper called?
Wilsons disease
neurological symptoms and liver pathology due to copper accumulation in tissues…. [Cu2+] is not bound by ceruloplasmin and so is improperly metabolised and excreted
What are steroid hormones derived from?
Cholesterol
What is thyroxine transported in the blood?
Bound to thyroid-binding globulin
What is cortisol transported in the blood?
Bound to cortisol-binding globulin
Describe lipoproteins?
Core of hydrophobic lipids
Surround by a shell (phospholipid, and apoproteins)
Free cholesterol dispersed throughout
Fat transport between organs and tissue
What is the function of HDL?
Reverse cholesterol transport
What is the function of LDL?
Cholesterol transport to peripheral tissues
Describe reverse cholesterol transport by HDL?
It removes excess cholesterol from cells
What is the liver the only organ capable of metabolising and excreting?
Cholesterol
When cholesterol is esterifed with fatty acids and transported back to the liver what does the liver do?
It excretes it as bile salts via the biliary system or faeces
What does the liver store?
Vitamins A, D and B12
Iron
Where does the iron stored in the liver come from?
The breakdown of haemoglobin, soared associated with ferritin
What is cholesterol as essential component of?
Mammalian cell membranes - increases the rigidity
What is cholesterol the precursor for?
Three important classes of biologically active compounds
- bile acids
- steroid hormones
- Vit D
Where is cholesterol stored?
It can be incorporated into lipoproteins and thus solubilised (located in the core of the molecule)
IT can be stored in lipid droplets
Majority of it is esterified to a wide range of long chain fatty acids
30% is circulating in free form
Where is cholesterol synthesised?
In virtually all cells
Mainly in the liver
What does synthesis of 1mol of cholesterol require?
Source of C atoms - 18mol of acetly-CoA
Source of reducing power - 16 mol of NADPH
Significant amounts of energy - 36mol of ATP
What does HMG-CoA reductase do?
Catalyses the irreversible formation of mevalonic acid
It is a rate limiting enzyme
What is HMG-CoA reductase a target for?
Cholesterol lowering drugs - statins
What is cholesterol synthesis controlled by?
Hormones
HMG-CoA reductase
Describe steroid hormones as a product of cholesterol?
Three groups
Corticosteroids (adrenal cortex)
Androgens (testis)
Estrogens (ovary)
What is the main metabolic product of cholesterol?
Bile salts
Where are bile salts synthesises and secreted by?
The liver
What do bile salts act as?
Dtgergents for emulsifying ingested lipids
What are bile salts recycled by?
The enterohepatic circulation
