Flashcards in Biochemical Aspects of Liver Metabolism Deck (77):
Where is the first destination of most nutrients and xenobiotics absorbed from the GI tract?
What does the liver produce?
Name a plasma protein excreted from the liver?
What two roles does the liver have in regulation of metabolism?
1. Carbohydrate and lipid metabolism - fuel storage
2. Amino acid metabolism - urea cycle
What allows seperation of proteins by size?
What 4 plasma proteins can be seperated by electrophoresis?
2. Alpha globulins
4. Gamma globulins
What substances maintan oncotic or colloid osmotic pressure?
What transports hydrophobic substances like steroid hormones, free fatty acids, bilirubin and cholesterol?
How can plasma proteins be involved with pH buffering?
Amino-acid side chains can carry net charges
What plasma proteins transport lipoproteins, lipids, hormones and bilirubin?
Alpha-globulins such as ceruloplasmin
What alpha-globulin, other than ceruloplasmin, transports vitamin A?
Retinol binding protein
What does deficiency of vitamin A cause?
What is vitamin A converted to?
Retinaldehyde, part of rhodopsin, a visual pigment
Name two beta-globulins?
Transferrin and fibrinogen
What two things does transferrin do?
Indicator of iron deficiency
What is an inactive form of fibrin and is involved in clotting of blood?
What is the most abundant plasma protein?
How would you describe albumin?
Small, negatively charged, water-soluble
What is the main determinant of plasma oncotic pressure?
What stimulates production of albumin in the liver?
What are levels of albumin like in liver disease?
What two factors can lead to low levels of albumin?
Starvation and low protein diets
What does albumin have multiple binding sites for?
What is the affinity and capacity like for albumin?
Low affinity, but high capacity because of high concentration
Name three endogenous lipophilic substances that albumin transports?
What important exogenous substances does albumin carry?
What special structural feature of albumin allows it to carry hydrophobic molecules?
Hydrophilic clefts in globular domains
What do haemoglobin, myoglobin and cytochromes all haev which is a key component?
How is iron transported?
As ferric ion Fe3+ bound ti transferrin
How is iron stored?
In cells bound to ferritin
What is an essential trace element?
How is copper transported?
In blood bound to ceruloplasmin
What disease is related to a copper/ceruloplasmin deficiency?
What are two hydrophobic hormones?
Steroid hormones (derived from cholesterol)
T3/T4 thyroid hormones
How is thyroxine transported?
Bound to thyroid-binding globulin
How is cortisol transported?
Bound to cortisol-binding globulin
What do transport proteins do to steroid hormones and T3/T4 thyroid hormones?
Extend biological half-life and increased plasma concentration
What two substances are in teh core of lipoproteins (core of hydrophobic lipids)?
Cholesterol esters and triglycerides
What two substances are in the shell of a lipoprotein?
Polar lipids and apoproteins
What substances are involved in fat transport between organs and tissues?
What is the density order for lipoproteins, starting with the least dense?
Chylomicrons, VLDL, IDL, LDL, HDL
Where do chylomicrons originate and what is there function?
Intestine - transport of exogenous fat to liver
Where does VLDL originate and what is its function?
Liver - transports endogenous fat to peripheral cells
Where does IDL originate and what is its function?
VLDL - LDL precursor
Where does LDL originate and what is its function?
VLDL/IDL/liver - cholesterol transport to peripheral tissues
Where does HDL originate and what is its function?
Intestine/liver - reverse cholesterol transport
What removes excess choleeterol from cells?
How is cholesterol removed from cells?
Esterified with fatty acids, transported back to liver, excreted as bile salts via biliary system or faeces
What is the only organ capable of metabolising and excreting cholesterol?
What vitamin does the liver store for 10 months as retinol palmitate?
What vitamin does the liver store for 3 weeks?
What vitamin is stored in hte liver for a few years worth?
What is cholesterol a precursor for (3 substances)?
1. Bile acids
2. Steroid hormones
3. Vitamin D
What is a major component of gall stones?
Where in cells is cholesterol synthesised?
In cytoplasm or enzymes bound to ER membranes
What other three organs, than the liver, are involved in cholesterol synthesis?
Intestine, adrenal cortex and gonads
What three things does synthesis of 1 mol of cholesterol require?
1. Source of C atoms
2. Source of reducing power
3. Significant energy
How many moles of acetyl-CoA is needed for 1 mol of cholesterol?
How many mol of NADPH is needed for 1 mol cholesterol?
How much energy is needed to make 1 mol of cholesterol?
36 mol of ATP
What converts HMG CoA to mevalonic acid in cholesterol synthesis?
What does HMG-CoA reductase catalyse?
The reversible formation of mevalonic acid, so is rate limiting
What is the synthesis and activity of HMG-CoA reductase stimulated by?
What does dietary cholesterol and high intrahepatocyte cholesterol do to HMG-CoA reductase?
What drugs target HMG-CoA reductase?
What product from cholesterol has a role in the regulation of calcium and phosphorus metabolism?
What is the most abundant form of vitamin D in the circulatory system?
Where are corticosteroids (21 carbon atoms) synthesised?
Where are androgens (19 carbon atoms) synthesised?
Where are oestrogens (18 carbon atoms) synthesised?
What is the main metabolic product of cholesterol?
Where are bile salts synthesised and stored?
Stored as compoennet of bile in gall baldder
What, once released into the duodenum, act as detergents for emulsifying ingested lipids?
What agents bind bile salts and inhibit reabsorption in the enterohepatic circulation?
Anion exchange resins - cholestyramine
What do anion exchange resins do to bile salt excretion and synthesis?
Increased bile salt excretion with increased synthesis of bile salts
When there is increased synthesis of bile salts in teh liver, what does the concentration of cholesterol do?
Decrease and number of LDL receptors of hepatic cells increases