abundant, liver

 It is soluble and monomeric. Albumin transports hormones, fatty acids, and other compounds, buffers pH, and maintains osmotic pressure, among other functions.

preproalbumin

This has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin.

chromsome 4.

mutations in this gene can result in anomalous proteins.

15

these are symmetrically placed within the 3 domains thought to have arisen by triplication of a single primordial domain.

true or false?

alpha helices are marginally stable in solution?

this is true. because of this they tend to be packed pairwise in proteins with hydrophibic residues pointing towards the molecules core.

eg Dimeric Rop protein - a small RNA binding protein that adopts a 4-helix bundle

1. as a transporter of smaller, mostly hydrophobic, molecules

2. it is the major contributor (80%) of the osmotic swelling pressure of blood plasma.

the positive electrode 

this is because at the pH of 7.4 found in the body, albumin is negatively charged. the glomerular basement membrane is also negatively charged in the body; some studies suggest that this prevents the filtration of albumin in the urine

Mr 66.500 daltons or 66.5kD

PI 5.67

HSA consists of a single polypeptide chain containing how many amino acids?

how many intrachain disulphide bonds are there?

the single polypeptide chain contains 585 amino acids and they are 17 intra-chain disulphide bonds

these disulphide bonds pull the molecule into a series of large (L) and (S) double loops.

three, domains, repetitions

possible evolution of HSA is thought to have started with a n original L gene > 2 duplications to LLL >1 mutation to LSL > a further 2 duplications to LSL - LSL - LSL (HSA)

nephrotic syndrome - a non specific disorder where the kidneys are damaged causing them to leak large amounts of protein from the blood into the urine. nephrotic sundrome patients are sometimes given albumin to replace the lost albumin.

name two unusual things about the sequence of albumin

clue :cysteine and charges on amino acids

1. it has a high percentage of Cystein residues (35 out of 585 amino acids)

2. high percentage of charged amino acids

the primary structure also contains a single free sulphydryl known as cysteine 34

it can bind ions of Cd, Au, Hg, Ag

the N-terminal 'His-3' binds Cu(II), Ni(II)

true or false?

Cu(II) transport in the blood is primarily as a complex with albumin and free His?

this is true.

in addition a number of hormones and drugs are transported including Aspirin, AZT, Penicillin and Warfarin.

pharmacoligally important as drugs compete for binding sites and small molecules not transported on proteins may be excreted by the kidney into the urine

within the hydrophobic residues of human serum albumin.

the general feauture of a globular protein is that hydrophobic residues are found in the interior whilst the hydrophillic residues are found on the outside.

Hypoalbuminemia

sick people have LOW levels of ambumin. the effect of administration of albumin is that the vast majority of sick people who get albumin get better.

It is used in treatment of cancer, autoimmune diseases and, ectopic pregnancies. It acts by inhibiting the metabolism of folic acid.

Methotrexate was originally developed for chemotherapy either alone or in combination with other agents. It is effective for the treatment of a number of cancers including: breast, head and neck, leukemia, lymphoma, lung, osteosarcoma, bladder, and trophoblastic neoplasms