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20 Cards in this Set
- Front
- Back
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Where and how is albumin made?
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Made as a preprotein with a signal sequence at the N-terminus passing through ER membrane to cisternae in liver. The signal peptide is removed by signal peptidase, and a hexapeptide sequence is further taken from the N-terminus.
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Describe the structure of albumin.
Function? How will it be represented in liver disease? |
Ellipsoid shape with 17 S-S bonds and 3 distinct domains.
A plasma protein generating osmotic pressure. Major transport molecule, e.g. for free fatty acids to tissues. Liver disease will show a decreased albumin/gamma-globulin ratio. |
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Name 2 ions albumin can carry.
Give examples of 4 drugs carried by albumin. Give examples of other substances carried by albumin. |
Calcium and copper. BUT...copper in principally carried by ceruloplasmin. Albumin binds copper less tightly = more important as a SUPPLIER.
Transports sulfonamides, penicillin G, dicumarol and ASA. Others: steroid hormones, bilirubin, tryptophan. |
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Describe the structure and role of ceruloplasmin.
What disease is it decreased in? |
Alpha-2 globulin binding copper, carrying 90% tightly so it is relatively inexchangeable.
Wilson's DX. |
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Outline the role of copper.
Where is it found? Too much? |
Metal cofactor for: SOD, lysyl oxidase, tyrosinase and cytochrome oxidase = involved in HYDROXYLATION, OXYGENATION and DISMUTATION.
Found in bone, liver, kidney and muscle. 100 mg total, 2-4 ingested daily, 1-2 are absorbed and bound to albumin. Too much: toxic! promotes oxidation of proteins and lipids and free-radical production. |
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Where does copper bind in cells?
What will be found with increased exposure to metallic ions? |
Binds to metallothioneins which have many cysteine residues (-SH) to bind with copper, zinc, cadmium and mercury. This holds them in a non-toxic form.
Increased metallothioneins levels. |
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What is Menke's disease?
What happens to the levels of copper-dependent enzyme activities? |
-X linked disorder of Cu metabolism.
-Involves NS, connective tissue and vasculature. -Mutation of copper binding P-type ATP-ase, preventing removal of ions in a tissue (move in via diffusion, move out via active transport) = tissue accumulation. Cu-dependent enzyme activities decrease = accumulation of inactive apoenzymes. |
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Is the liver affected in Menke's disease?
How is Menke's disease marked? Name another enzyme affected. |
No - liver has a different copper binding ATPase.
Marked by depressed serum Cu and ceruloplasm, and elevated intestinal and kidney Cu. Lysyl oxidase is affected - a problem because it is needed to post-translationally modify collagen. |
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What is Wilson's disease?
What is the Kayser-Fleishcher ring? Diagnose it! |
-Involves ATPase type found in liver.
-Increased levels of cu in liver, brain, kidney and rbc. -Cu not secreted into bile -Increase liver Cu leads to poor coupling to cerulopasmin and fall in cerulopasmin levels. Leads to: hemolytic anemia, cirrhosis or hepatitis and neurologic syndrome (Cu accumulates in basal ganglia). Ring: greenish-gold ring seen in cornea due to copper deposition. Diagnosed: with liver copper > 250 ug/day and ceruloplasmin < 20 mg/day. Elevated urinary copper. |
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List some other consequences of Wilson's disease.
How is this acquired? Tx? |
-Impaired bilary Cu secretion
-Reduced Cu binding to apoceruloplasmin and Cu accumulation in liver and brain. Genetically: autosomal recessive, later onset than Menkes. Tx: low Cu diet, penicillamine which chelates Cu so it can be removed as a complex in urine. |
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What are the 2 broad classes of protein shape?
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Globular: compact, folded proteins. E.g. albumin. Fold together to give 3-D shape. AA sequence (primary structure)
Fibrous: extended filaments, cable-like. |
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What is the secondary structure of a protein? What are the 2 broad classes?
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Secondary structure: part of the linear sequence of amino acids.
2 types: alpha-helix, a cylinder. E.g. myoglobin - composed of 8 alpha helices, separated by turns. Beta-sheet - linear series of aa fully extending. Enzyme trios phosphate isomerase is a mixture of beta-sheets and alpha-helices. This is known as a barrel. |
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What determines the final shape of the protein?
How was this tested? |
Final shape is determined by the nature of the aa sequence.
Tested using ribonuclease A. This was denatured = configuration lost in presence of an agent such as urea. This blocks the ability of the protein to fold. If urea is removed, ribonuclease molecules can return to original shape, as folding patterns are encoded in aa sequence. |
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Give the factors that drive protein folding.
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-Proteins fold so they assume a relatively stable position = E release.
-Favourable conformation occurs with favourable interactions between protein groups. E.g. 1 a-helix is stabilized by sharing of H atoms between aa of helix. H bonds also formed between beta-sheets. E.g. 2: oppositely charged groups can come together to form a salt bridge to stabilize protein confirmation. E.g. 3: van der Waal's F. - weak interactions b/w adjacent atoms. - Hydrophobic effect: side chains of hydrophilic chains orient on surface, while hydrophobic orient toward inside of protein. |
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What are 2 problems with protein folding?
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1) If protein is large, finding correct protein can be a challenge
2) Protein sequence emerges gradually - as they are extruded as a growing protein chain from ribosome-mRNA complex. In this case, the hydrophobic side chains can stick together in the presence of water before there may be proper folding, this is alleviated by the use of CHAPERONES - bind with newly formed proteins or provide cavities. |
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The sequence of aa in fibrous proteins favours a particular secondary structures that confer structural properties on the fibrous protein. Give 3 examples of fibrous protein.
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1) Alpha-keratins
2) Silk fibroin 3) Collagen |
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Alpha Keratins:
Where are they found? How does this structure exist? Where are hydrophobic aa found? How many aa/turn? Overall structure due to interactions? |
Found: skin, hair, nails, intermediate filaments in cells.
Exists: not as a single molecule, but coiled around each other in a coiled-coiled structure. Hydrophobic aa: every 4th side chain. 3.6 aa/per turn = there is a line of hydrophobic side chains along one side of each alpha-helix. Overall: hydrophobic side chains down the middle forms an adhesive strip allowing 2 alpha-keratins associated by wrapping around each other, forming a coiled-coil structure. |
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Describe the structure of an alpha-helix. (In terms of protofialments, microfibril structure, etc).
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-Distinctive n-terminal and c-terminal domains interacting to form protofilaments composed of a continuous array of dimers.
Dimers form protofibrils, which are units of microfibril structure. a-keratins have high cys content, and -SH side chains permit x-linkages between cys side groups via S-S bridges. More cross linking = more strength = horn, nails > hair > skin. E.g. wool. |
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Silk fibroin:
What secondary structure is present? Which aa are richest? What is the strength attributed to? What types of bonds are within sheets? How is stretchiness generated? |
Secondary structure: beta-pleated sheets, not helices.
Righest in glycine and alanine. THese have small side chains which can interdigiate b/w beta-pleated structures. Strength is attributed to fact that beta- sheets are fully extended, and cannot be further stretched, but remains flexible. Covalent bonds found within sheets. Steretchiness comes from regions with aa with bulkier side chains that interrupt beta-chain structure. |
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Collagen:
Basic unit? What's glycine got to do with it? |
Basic unit: tropocollagen, consisting of a triple helix of 3 collagen chains. Repetative glycine-x-y sequence, where x is often proline and y is often hydroxyproline.
Glycine has a small side group (-H) that can fit in the centre of the triple helix without disrupting structure. |
