TBPP_albumin

synthesis in the liver (10-15g/day), most abundant protein in plasma (35-50g/L, 50%), second most abundant protein in the body (4-5g/kg) ca. 350g total, 40% intravascular and 60% extravascular, half life: 20 days

kidneys (10%), large organs/muscle/skin (80%), gastro intestinal tract (10%), broken down into AS

diffusion of fluid through semi-permeable membrane from a solution with a low solute concentration (hypotonic) to a solution with a higher solute concentration (hypertonic) until equal concentration on both sides. Osmotic: degree of osomotic force produced by fluid. Oncotic: osmotic force caused by protein in plasma.

water, albumin, electrolytes. Intra- and extravascular space, extra- and intracellular space, interstitial space. Fluid balance: normal distribution of water and its solutes within different compartments, essential to health.

separates intra- and extravascular space, 7-9 micrometre in diameter, one cell thick, as semi-permeable membrane

COP is the major fluid shifting force pulling fluid into intravascular space, COP attracts fluid into the blood vessel at venule end of capillary, COP exerted by colloids (albumin), also oncotic pressure. 90% resorption, 10% goes to the lymph by hydrostatic pressure.

high pressure at arterial end of capillaries pushes liquid and nutrients into interstitial space (then to tissues). Albumin contributes 80% of the COP in blood, negative charge: retention of diffusable ions, albumin retains 18ml of water per gramm, 20L of fluid to interstitial space per day

shifts in the distribution of water, salt and protein in the body, during first 24h: increase of permeability of blood vessels and this leads to loss of salts, water and proteins. After 24h: capillary less leaky. Results in: decrease in plasma volume/COP, increase in tissue fluid (oedema).

albumin synthesised in liver, liver cirrhosis: damage to hepatocytes = reduced albumin synthesis, water retention: dilution of albumin = Hypoalbuminaemia

transport/delivery, detoxification, reservoir for signalling molecules, acid-base balance, apoptosis, cell proliferation, oxidation-reduction, immunomodulation.

many functions mediated by ligand binding, multiple specific binding sites for: FS, Bilirubin, Copper (Cu), Heme, Calcium, NO, Vitamins, drugs, toxins etc.

detoxification of bilirubin. Binding bilirubin to albumin --> solubilisation and neutralization --> transport to the liver for excretion. Heme --> biliverdin --> bilirubin. Conjugation: attachment of glucuronic acid by glucuronyltransferase. In neonates bilirubin can raise and cause jaundice. phototherapy: light sensitivity causes isomerization to lumirubin = more soluble in plasma and excreted in kidney.

FS essential for: energy metabolism, synthesis of membrane. Albumin: binds and solubilizes up to 7 FS, main protein binding FS in fluids, delivery to vascular endothelium, interstitial: transport to tissues.

toxicological relevance (Ni2+, Co2+, Cu2+ etc.), majority of copper bound to ceruloplasmin (redox protein responsible to Fe2+ to Fe3+ to enable Fe binding to transferrin), 4 metal binding sites (N-terminal, cys34, multiple metal binding site, site B). N-terminal: DAHK = penta coordinated Cu2+, 4 nitrogen ligands in equatorial position, apical oxygen by H2O, high-affinity binding, this arrangement prefers squareplanar complex formation

1941 plasma from american red cross, all albumin stock burnt during pearl harbor attack, large expansion of programm, commercialization in Europe started in 1945

base fractionation: 1. ethanol precipitation: Ig, 2. ethanol precipitation: Fraction IV, 3. ethanol precipitation: albumin precipitate. Bulk facturing: mince precipitate and dissolution --> clarifying filtration --> ultra- and diafiltration --> formulation (stabilizers, pH etc.). filtration and ending: albumin bulk --> sterile filtration --> aseptic filling --> pasteurization --> incubation --> visual inspecting --> final product. Heat treatment: for 10h at 60°C, stabilizer: sodium octanoate/sodium acetyltryptophanate: increase of thermal stability.