[Taxikk]

Hello, everyone! Could you please answer on some questions.

I want to know about a bilirubin-albumin bond and penetration of blood brain barrier(BBB) of the healthy adult(not infant). I have some questions:
1) I read that unconjugated bilirubin is bound with albumin don't penetrate in tissue. Then why does human become yellow with elevated levels of bilirubin(eg 5 mg/dL, albumin can bind 20-25 mg/dL) and normal level of albumin?
2) In the books written that unconjugated bilirubin even with severe and long-standing jaundice can't penetrate the adult brain. Then why human who has >2-3 mg/dL of bilirubin feels neurological symptoms?
3) Can unbound unconjugated bilirubin(without albumin bond) penetrate in the adult brain? If it can, why and when? And what level is it? (P.S. I read that the BBB is impenetrable for molecules with molar mass over 500, bilirubin has 584 molar mass. Also that the bilirubin level about 60 mg/dL caused no apparent disruption in brain energy metabolism)

[Arkcon]

What, specifically, are the neurological effects caused by the deposition of biliruben in tissues?  As is said here: jaundice, the visual effect of bilruben deposition, is a symptom, and not a cause:  https://en.wikipedia.org/wiki/Jaundice#Pathophysiology  So maybe something else is causing neurological effects?

[Babcock_Hall]

@ OP, How is bilirubin bound to serum albumin?

[Taxikk]

What, specifically, are the neurological effects caused by the deposition of biliruben in tissues?  As is said here: jaundice, the visual effect of bilruben deposition, is a symptom, and not a cause:  https://en.wikipedia.org/wiki/Jaundice#Pathophysiology  So maybe something else is causing neurological effects?

I mean neurotoxic effects of bilirubin: lethargy, drowsiness, apathy, dizziness...

[Taxikk]

@ OP, How is bilirubin bound to serum albumin?

http://www.jbc.org/content/258/10/6319.full.pdf
http://www.ebi.ac.uk/biomodels-main/static-pages.do?page=ModelMonth%2F2012-10
http://www.ncbi.nlm.nih.gov/pubmed/1157293

[Babcock_Hall]

You originally wrote, "I want to know about a bilirubin-albumin bond..."  I now assume that you understand that this is a non covalent interaction.

[Pastychomper]

... I read that the BBB is impenetrable for molecules with molar mass over 500, bilirubin has 584 molar mass....)

That is a rule of thumb but there are other important factors, including lipophilicity and number of hydrogen-bonding groups. 

Just going by the structure, bilirubin has several polar groups including two acids, so I'd expect it to show little brain penetration - but 'little' doesn't necessarily mean 'none' and there may be other factors (such as interaction with transporters or other molecules at the BBB).

 This paper (1978) proposed a mechanism for bilirubin to cross the BBB, and this site mentions the possibility of a damaged or immature BBB allowing it to pass.

[Taxikk]

Just going by the structure, bilirubin has several polar groups including two acids, so I'd expect it to show little brain penetration - but 'little' doesn't necessarily mean 'none'...

Then a human with normal level of bilirubin also has brain penetration, little but it has.
So why in the all books is written that bilibrubin don't penetrate in a healthy brain?

[Taxikk]

...is a non covalent interaction.

What do you mean? Please tell more informative.
Did you mean about equilibrium concentration? That there is always small concentration of unbound-bilirubin in blood?

[Babcock_Hall]

By non covalent, I simply mean that the process involves weak intermolecular forces.  I do not mean that the dissociation constant has any particular value.  For example, the binding of GTP to ras p21 and the dissociation constants of methotrexate to dihydrofolate reductase are both in the general vicinity of 1 nano molar, possibly smaller, yet they are not covalent interactions.  With respect to serum albumin, phenol red binds strongly, but to the best of my knowledge, this interaction is also non covalent.  I don't know the value of the dissociation constant with respect to billirubin.