Albumin is the most prevalent protein in human blood. It's also huge, and shouldn't leak from healthy endothelium. But it is also a sponge in the sense it can bind to a huge array of oxidaised molecules (anti oxidant), drugs, steroid based drugs/hormones/antibiotics
and of course anaesthetic! Inflammation and cell stress generally promote systemic protease activity and albumin is fragmented (uraemia has a similar affect on albumin). Hence SIRS patients have heavy albumin losses and replacing it doesn't work :p
They do lose production also via reduced liver synthetic function but that's usually a late feature - the early loss is like albumin haemolysis. Oxidised albumin can be measured in mum/baby blood of pre-eclamptics and will prognosticate.
Glycosylation is another interesting physical change to molecules that affect function. The glycosylation pattern on CRP can help tell you if CRP is from sterile or infected source, and sometimes which organ. We are familiar with it in diabetes and test haemoglobin for that!
Glycosylation of albumin really interferes with its binding. This removes anti oxidant potential and also enhances the free portion of serum drugs. I checked if this affects propofol (it does) but actually for the TCI infusions, more is also excreted and redistributed so
it doesn't modify overmuch. Apparently. However this leads on to find that plenty of diseases affect the glycosylation of molecules. This actually breeds a whole field of molecular path called the glycome. For example COPD patients have a signature glycome.
Then I checked in cardiac surgery (this is a great model for SIRS because patients have near perfect scripted 24-72 hours of profound SIRS which either pootles off or causes havoc) and yes IgG glycoforms will predict mortality. https://www.nature.com/articles/srep04347
So unclear if cause/effect/both but does seem glycosylation (sugar chains) --> loss of homeostasis that promotes unusual molecule-molecule interactions, like me when my hair catches on branches out horse riding.
Apparently we don't know much about how it is driven or controlled and much diversity - e.g. ser/threonine residues alone may have 10 million sugars. 9 amino acids will become glycolsyated.
But some individual interactions are important e.g. ganglioside-glycosylation on the insulin receptor is v susceptible to TNFa signalling leading to loss of insulin sensitivity during inflammation :(
You can follow @Jopo_dr.
Tip: mention @twtextapp on a Twitter thread with the keyword “unroll” to get a link to it.

Latest Threads Unrolled: