Biochemistry of the Liver Flashcards
What is the role of Cytochrome p450?
metabolises potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin principally in the liver
Roles of the liver?
First destination of most nutrients and xenobiotics absorbed from the GI tract
Bile production
Elimination of unwanted molecules
Secretion of plasma proteins
e.g. albumin
Storage of important molecules
e.g. fuels, iron, vitamins
Regulation of metabolism
carbohydrate and lipid metabolism - fuel storage
amino acid metabolism - urea cycleHow are proteins seperated by size?
Electrophoresis
What are the main functions of plasma proteins?
Maintenance of oncotic or colloid osmotic pressure
- don’t exit into interstitial fluid
- prevents loss of plasma proteins
Transport of hydrophobic substances
- steroid hormones, free fatty acids, bilirubin, cholesterol
pH buffering
- amino acid side chains can carry net charges
Enzymatic
- e.g. blood clotting
Immunity
How does the oncotic force act?
draws fluid from body compartments to the blood
What controls oncotic pressure?
Albumin
What is the role of alpha gobulin?
transport lipoproteins, lipids, hormones and bilirubin
retinol binding protein - ceruloplasmin
- transports vitamin A
What does vitamin A deficiency result in?
visual impairment
lipid soluble alcohol, converted to retinaldehyde, part of rhodopsin, a visual pigment
Name two types of beta gobulins?
transferrin
- transports Fe3+
- indicator of iron deficiency
fibrinogen
- inactive form of fibrin
- clotting of blood
What is the most abundant plasma protein?
Albumin
How much Albumin does the liver normally make each day?
14 g/day
What stimulates Albumin production? What can cause it to drop?
insulin stimulates production
starvation/low protein diet causes decrease of levels - levels are low in liver disease
Which endogenous and exogenous substances does Albumin transport?
transports important endogenous lipophilic substances e.g. fatty acids, distribution of energy-rich substrates, bilirubin, breakdown product of haem, thyroid hormones
transports important exogenous substances e.g.
drugs like aspirin (any drug that has a weak hydrophobic capacity)
Describe the transport mechanisms of Albumin?
Multiple binding sites for hydrophobic molecules
hydrophobic clefts in globular domains
low affinity, but high capacity because of high concentration
Transports endogenous and exogenous substances
How is iron transported?
as ferric ion Fe3+
bound to transferrin
How is iron stored in cells?
bound to ferritin
How is copper transported in the blood?
bound to ceruloplasmin
What is Wilson’s Disease?
Copper deficiency
Are Steroid hormones and the T3/T4 thyroid hormones hydrophobic or hydrophillic?
hydrophobic
How is thyroxine transported in the blood?
bound to thyroid-binding globulin
How is cortisol transported in the blood?
bound to cortisol-binding globulin
Describe the make up of lipoproteins?
Core of hydrophobic lipids
cholesterol esters
triglycerides
Surrounded by shell
polar lipids (phospholipids)
apoproteins
Free cholesterol dispersed throughoutWhat is the function of HDL?
Removes excess cholesterol from cells
- cholesterol is esterified with fatty acids
- transported back to liver
- excreted as bile salts via biliary system or faeces
Which organ can control cholesterol levels?
liver
What is cholesterol a precursor of?
bile acids
steroid hormones
vitamin D
What is cholesterol metabolism important for?
etiology of cardiovascular disease
major component of gall stones
Where is cholesterol stored?
lipid droplets
How is cholesterol transported in water?
30 % of circulating cholesterol is in free form
Majority is esterified to a wide range of long-chain fatty acids
- through hydroxyl group
- even less soluble in water
How is cholesterol solubilised?
is incorporated into lipoproteins
Where is the main and lesser sites of cholesterol synthesis?
- liver
Lesser: intestine, adrenal cortex, gonads
What does the synthesis of 1 mol cholesterol require?
source of C atoms
18 mol of acetyl-CoA
source of reducing power
16 mol of NADPH
significant amounts of energy
36 mol of ATPWhat is the role of HMG-CoA reductase?
Catalyses the irreversible formation of mevalonic acid
What reduces HMG-CoA reductase activtiy?
Dietary cholesterol and high intrahepatocyte cholesterol
What stimulates HMG-CoA reductase activity?
fasting
What is the most abundant form of vitamin D in the circulatory system?
Vitamin D3
What is the role of vitamin D?
regulation of calcium and phosphorus metabolism
What are the three groups of steroid hormones?
corticosteroids
androgens
estrogens
Where are corticosteroids, androgens and estrogens released?
corticosteroids - adrenal cortex
androgens - testis
estrogens - ovary
How are primary bile salts converted to secondary bile salts?
bacteria in the intestine
Describe the life cycle of bile salts?
Synthesised and secreted by liver
Stored as component of bile in the gall bladder
Once released into the duodenum, act as detergents for emulsifying ingested lipids
Recycled by enterohepatic circulation
How is cholesterol excretion manipulated?
Anion exchange resins (e.g. cholestyramine) bind bile salts and inhibit reabsorption in the enterohepatic circulation
Increased bile salt excretion and synthesis of bile salts
Concentration of cholesterol in the liver is decreased
The number of LDL receptors of hepatic cells increases
Uptake of LDL cholesterol from plasma increases
Lower plasma LDL and therefore cholesterol
