Biochemistry of the Liver Flashcards
what are the 6 functions of the liver?
first destination of most nutrients/xenobiotics absorbed from GI tract
Bile production
Elimination of unwanted molecules (metabolism, excretion)
Secretion of plasma proteins (albumin)
Storage of important molecules (fuel, iron, Vitamins)
Regulate metabolism
what might be sign of liver disease in the faeces?
pale stools (not breaking down haemoglobin into bilirubin which colours faeces)
which 2 processes of metabolism is the liver linked to?
carbohydrate and lipids = fuel storage
amino acid = urea cycle
what is electrophoresis?
separation of proteins (in blood plasma) by size
what are the functions of plasma proteins?
maintain oncotic or colloid osmotic pressure (hydration, BP regulation)
Transport hydrophobic substances (steroid hormones, free fatty acids, bilirubin, cholesterol)
pH buffering
Enzymatic - blood clotting
Immunity
what does albumin do?
oncotic pressure, BP, transport substances etc
what do alpha globulins do?
transport lipoproteins, lipids, hormones and bilirubin
retinol binding protein (transports Vit A)
Eg. ceruloplasmin
Name 2 Beta globulins and their functions
transferrin - transfers Fe3+ - indicator of iron deficiency Fibrinogen - inactive form of fibrin - clotting of blood
what is the most abundant plasma protein?
albumin (50%)
liver synthesises 14g pe3r day
what controls synthesis of albumin?
hormones (eg. those released in response to a meal - insulin etc)
what can cause low levels of albumin?
liver disease
starvation/low protein diet
albumin is negatively charged and water soluble, true or false?
true
albumin transports which lipophilic substances?
fatty acids
bilirubin
thyroid hormones
what exogenous substances does albumin transport?
drugs like aspirin
albumin has low affinity for hydrophobic molecules, how do they have a large transport capacity?
high concentration
multiple binding sites
how is iron transported in the body?
as ferric ion Fe3+ (bound to transferrin)
how is iron stored?
stored in Fe2+ form in cells bound to ferritin (can be oxidised to Fe3+ to be released and used again)
what processes is iron involved in?
component of haemoglobin, myoglobin, cytochromes
which redox reaction is redox of iron linked to?
copper
how is copper transported in the body?
bound to ceruloplasmin
what results from a copper deficiency?
Wilson’s disease
name some hydrophobic hormones
steroid hormones (derived from cholesterol) T3/T4 thyroid hormones
how are hydrophobic hormones transported in the body?
bound to specific transport molecules
- thyroxine bound to thyroid binding globulin
- cortisol bound to cortisol binding globulin
why are transport proteins important for hydrophobic proteins?
would be eliminated by liver/kidney without them
extend half life and increase plasma conc
describe the structure of lipoproteins
core of hydrophobic lipids surrounded by shell
free cholesterol dispersed throughout
what is the function of lipoproteins?
fat transport between organs and tissues
what is the function of LDL?
cholesterol transport to peripheral tissues
what is the function of HDL?
reverse cholesterol transport
removes excess cholesterol from cells, transported back to liver and excreted as bile salts via biliary system or faeces
which organ is capable of metabolising and excreting cholesterol?
only the liver
what substances does the liver store?
Vit A, D, B12
Iron
where does iron come from?
breakdown of haemoglobin, stored associated with ferritin
cholesterol is the precursor for which 3 compounds?
bile acids
steroid hormones
Vitamin D
what is the function of cholesterol?
increase rigidity of mammalian cell membranes
cholesterol metabolism is important in which 2 diseases?
cardiovascular disease
Development of gall stones
how is cholesterol transported in the body?
most esterified to long chain fatty acids
30% in free form
Low solubility in water
how is cholesterol stored?
incorporated into core of lipoproteins and solubilised, stored in lipid droplets
describe the structure of cholesterol
sterol ring
what is required for the synthesis of cholesterol in the liver?
18 mol acetyl CoA (C atoms)
16 mol NADPH (reducing power)
36 mol ATP (energy)
what is the rate limiting enzyme in cholesterol synthesis?
HMG-CoA reductase
controls production of precursor mevalonic acid
what increases/decreases activity of HMG-CoA reductase?
stimulated by fasting
inhibited by dietary/intrahepatocyte cholesterol
Target of statins
what are the products from cholesterol?
Vit D Steroid hormones (corticosteroids, androgens, estrogens) Bile salts (main metabolic product)
what is the process through which drugs lower plasma LDL?
bind bile salts and inhibit reabsorption in enterohepatic circulation
Increased bile salt excretion/synthesis
Cholesterol conc in liver decreases
Number of LDL receptors of hepatic cells increases
Uptake of LDL from plasma increases
what is the role of cytochrome P450?
detoxifying in the liver
