Flashcards in Biochemical Aspects of Liver Metabolism Deck (77):
1
Where is the first destination of most nutrients and xenobiotics absorbed from the GI tract?
Liver
2
What does the liver produce?
Bile
3
Name a plasma protein excreted from the liver?
Albumin
4
What two roles does the liver have in regulation of metabolism?
1. Carbohydrate and lipid metabolism - fuel storage
2. Amino acid metabolism - urea cycle
5
What allows seperation of proteins by size?
Electrophoresis
6
What 4 plasma proteins can be seperated by electrophoresis?
1. Albumin
2. Alpha globulins
3. Beta-globulins
4. Gamma globulins
7
What substances maintan oncotic or colloid osmotic pressure?
Plasma proteins
8
What transports hydrophobic substances like steroid hormones, free fatty acids, bilirubin and cholesterol?
Plasma proteins
9
How can plasma proteins be involved with pH buffering?
Amino-acid side chains can carry net charges
10
What plasma proteins transport lipoproteins, lipids, hormones and bilirubin?
Alpha-globulins such as ceruloplasmin
11
What alpha-globulin, other than ceruloplasmin, transports vitamin A?
Retinol binding protein
12
What does deficiency of vitamin A cause?
Visual impairment
13
What is vitamin A converted to?
Retinaldehyde, part of rhodopsin, a visual pigment
14
Name two beta-globulins?
Transferrin and fibrinogen
15
What two things does transferrin do?
Transports Fe3+
Indicator of iron deficiency
16
What is an inactive form of fibrin and is involved in clotting of blood?
Fibrinogen
17
What is the most abundant plasma protein?
Albumin
18
How would you describe albumin?
Small, negatively charged, water-soluble
19
What is the main determinant of plasma oncotic pressure?
Albumin
20
What stimulates production of albumin in the liver?
Insulin
21
What are levels of albumin like in liver disease?
Low
22
What two factors can lead to low levels of albumin?
Starvation and low protein diets
23
What does albumin have multiple binding sites for?
Hydrophobic molecules
24
What is the affinity and capacity like for albumin?
Low affinity, but high capacity because of high concentration
25
Name three endogenous lipophilic substances that albumin transports?
Fatty acids
Bilirubin
Thyroid hormones
26
What important exogenous substances does albumin carry?
Aspirin
27
What special structural feature of albumin allows it to carry hydrophobic molecules?
Hydrophilic clefts in globular domains
28
What do haemoglobin, myoglobin and cytochromes all haev which is a key component?
Iron
29
How is iron transported?
As ferric ion Fe3+ bound ti transferrin
30
How is iron stored?
In cells bound to ferritin
31
What is an essential trace element?
Copper
32
How is copper transported?
In blood bound to ceruloplasmin
33
What disease is related to a copper/ceruloplasmin deficiency?
Wilsons disease
34
What are two hydrophobic hormones?
Steroid hormones (derived from cholesterol)
T3/T4 thyroid hormones
35
How is thyroxine transported?
Bound to thyroid-binding globulin
36
How is cortisol transported?
Bound to cortisol-binding globulin
37
What do transport proteins do to steroid hormones and T3/T4 thyroid hormones?
Extend biological half-life and increased plasma concentration
38
What two substances are in teh core of lipoproteins (core of hydrophobic lipids)?
Cholesterol esters and triglycerides
39
What two substances are in the shell of a lipoprotein?
Polar lipids and apoproteins
40
What substances are involved in fat transport between organs and tissues?
Lipoproteins
41
What is the density order for lipoproteins, starting with the least dense?
Chylomicrons, VLDL, IDL, LDL, HDL
42
Where do chylomicrons originate and what is there function?
Intestine - transport of exogenous fat to liver
43
Where does VLDL originate and what is its function?
Liver - transports endogenous fat to peripheral cells
44
Where does IDL originate and what is its function?
VLDL - LDL precursor
45
Where does LDL originate and what is its function?
VLDL/IDL/liver - cholesterol transport to peripheral tissues
46
Where does HDL originate and what is its function?
Intestine/liver - reverse cholesterol transport
47
What removes excess choleeterol from cells?
HDL
48
How is cholesterol removed from cells?
Esterified with fatty acids, transported back to liver, excreted as bile salts via biliary system or faeces
49
What is the only organ capable of metabolising and excreting cholesterol?
Liver
50
What vitamin does the liver store for 10 months as retinol palmitate?
Vitamin A
51
What vitamin does the liver store for 3 weeks?
Vitamin Dq
52
What vitamin is stored in hte liver for a few years worth?
Vitamin B12
53
What is cholesterol a precursor for (3 substances)?
1. Bile acids
2. Steroid hormones
3. Vitamin D
54
What is a major component of gall stones?
Cholesterol
55
Where in cells is cholesterol synthesised?
In cytoplasm or enzymes bound to ER membranes
56
What other three organs, than the liver, are involved in cholesterol synthesis?
Intestine, adrenal cortex and gonads
57
What three things does synthesis of 1 mol of cholesterol require?
1. Source of C atoms
2. Source of reducing power
3. Significant energy
58
How many moles of acetyl-CoA is needed for 1 mol of cholesterol?
18 mol
59
How many mol of NADPH is needed for 1 mol cholesterol?
16 mol
60
How much energy is needed to make 1 mol of cholesterol?
36 mol of ATP
61
What converts HMG CoA to mevalonic acid in cholesterol synthesis?
HMG-CoA reductase
62
What does HMG-CoA reductase catalyse?
The reversible formation of mevalonic acid, so is rate limiting
63
What is the synthesis and activity of HMG-CoA reductase stimulated by?
Fasting
64
What does dietary cholesterol and high intrahepatocyte cholesterol do to HMG-CoA reductase?
Reduces activity
65
What drugs target HMG-CoA reductase?
Statins
66
What product from cholesterol has a role in the regulation of calcium and phosphorus metabolism?
Vitamin D
67
What is the most abundant form of vitamin D in the circulatory system?
Vitamin D3
68
Where are corticosteroids (21 carbon atoms) synthesised?
Adrenal cortex
69
Where are androgens (19 carbon atoms) synthesised?
In testis
70
Where are oestrogens (18 carbon atoms) synthesised?
In ovaries
71
What is the main metabolic product of cholesterol?
Bile salts
72
Where are bile salts synthesised and stored?
In liver
Stored as compoennet of bile in gall baldder
73
What, once released into the duodenum, act as detergents for emulsifying ingested lipids?
Bile salts
74
What agents bind bile salts and inhibit reabsorption in the enterohepatic circulation?
Anion exchange resins - cholestyramine
75
What do anion exchange resins do to bile salt excretion and synthesis?
Increased bile salt excretion with increased synthesis of bile salts
76
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
77