Proteins - Serum Albumin Flashcards
Serum Albumin
This is a blood protein carrying many bioactive molecules in the blood(proteins, peptides, FA, hormones etc) in the blood, being a critical transport molecule.
What are the functions of Serum Albumin?
ROS scavenging
Transport smaller, hydrophobic molecules
Contributes 80% to osmotic swelling pressure of blood plasma
What is the synthesis pathway of Serum Albumin?
Synthesis occurs in the liver, maturing in the ER and Golgi then secretion from hepatocytes.
What is the concentration of albumin in the blood?
40g/L
What are the 2D structures of Serum Albumin?
Water-soluble, anionin globular protein with a 66.5 kDa with 585AA and 17 disulfide bonds
What is the 3D structure of the serum albumin?
11 Hydrophobic binding domains so can carry multiple FA
Three similar domains each with two domains, each with one long-alpha helix and many beta sheets.
Disulphide Bonds
These are covalent interactions between the sulfur atoms of two cysteine residues.
What amino acid residues are important for FA binding?
Tryptophan and Phenylalanine
How does fatty acid binding affect structure of Serum Albumin?
Conformational changes when FA binds hydrophobic cavity causing AA shifts forming new H-bonds and VDW interactions.
What does FA binding cause?
Increased albumin compaction due to hydrophobic interactions between FA protein hydrophobic residues.
FA tail buried within hydrophobic cavity in the protein, in tandem with head group hydrophilic interactions with polar amino acids.
Why do fatty acids require carrier molecules?
Fatty acids have high hydrophobicity.
Alpha Helicies
These are rod-like structures with inner sections of a tightly-coiled main chain and side chains extending outwards in a helical fashion.
What stabilises Alpha Helicies?
CO and NH hydrogen bonding
How is the hydrophobic cavity formed?
Orientiation of non-polar side chain towards the core.
What determines ligand-binding sites for molecules?
Conformation/Arragnement of alpha helicies.
Why are disulphide bonds important?
Maintenance of tertiary structure to prvent unfolding or misfolding.
Cysteine Knot
This is a knot that forms when disulphide bonds between cysteine 34 and 97, crossing the loop formed by the two with other disulfphide bonds.
How much of Serum Albumin is cysteine?
35 out of 585 AA
What is importance of free sulfhydryl at Cys-34 in reduced form?
Redox chemistry(when reduced, this group is free and highly reactive to oxidation)
Antioxidant
These are compounds able to neutralise free radicals like oxygen, nitrogen and lipids.
What can the Cys-34 bind?
Cd, Au, Hg and Ah ions.
What structures do the ligand binding sites include?
Heterocylci, aromatic, carboxylic acids and metals.
What does the His-3 Residue bind?
Transition metals
Transition metals
These are described as having great melting points, hardness and electrical conducitivty(Cu, Ru, Fe and Co)
What is the primary transported of Cu(II)?
Serum albumin.
What is the 3D structure of serum albumin?
Heart-shaped perturbed with FA binding.
Co-Ordination Bonds
These are covalent bonds where both electrons come from the same atom
How is serum albumin used in drug delivery?
Passive Diffusion
Receptor-Mediated Endocytosis
Albumin-Mediated Trasnport
Why is Serum Albumin good for drug delivery?
It has capacity to bind many drugs in bloodstream.
Receptor-Mediated Endocytosis
This is internalisation of ligands in clathrin-coated pits by binding to cell receptors.
Albumin-Mediated Transport
This is binding of drug to albumin through chemical conjugation(or nanoparticles/liposomes), targeted to tissues/organs.
Why are forest plots important?
Meta-analysis of drug/treatment effects using studies analyising the same thing and showing the outcome of each then adding them togtehr.
How are Forest Plots measured?
Odds Ratio
What are the Odds Ratio?
OR=1 No Effect
OR>1 Test better than control
OR<1 = Control better than test
What do the vertical/horizontal axis of forest plots depict?
Names of studies and effect estimates for each study.
