A yellow component associated with human transthyretin has properties like a pterin derivative, 7,8‐dihydropterin‐6‐carboxaldehyde

Abstract

Transthyretin (TTR) in plasma is associated with yellow compounds. Their properties differ, and in the chicken protein a major yellow compound has recently been identified as a carotenoid, lutein, also called xanthophyll. We now show that the major yellow component extracted from human TTR has properties like a pterin derivative, 7,8-dihydropterin-6-carboxyaldehyde (2-amino-4-hydroxy-6-formyl-7,8-dihydropteridine). The human TTR derivative has chromatographic and spectral properties identical to a yellow photochemical degradation product of biopterin and a spectrum like that of the pterin aldehyde.

Aboard transthyretin: From transport to cleavage

“…Lutein binding to chicken TTR was shown to be specific and, as such, carotenoids were recognized as TTR ligands (38). In human TTR, the yellow component was described as being a pterin-derivate (interestingly, pterins are cofactors in the synthesis of catecholamines) (39). However, the presence of carotenoid-derived components could not be excluded.…”

Use of a 13C tracer to investigate lutein as a ligand for plasma transthyretin in humans

“…However, this explanation was discounted since previous investigators were able to isolate the yellow component from human plasma TTR that was similarly purified by RBP-Sepharose affinity chromatography. In these previous studies, human serum was directly applied to the affinity column without initial purification (16,23,36), resulting in minor contamination of the TTR fraction with RBP and other minor impurities. The presence of RBP is reported to be important in keeping a fraction of TTR in the reduced state (36), which may be a requisite for retention of the yellow component (16).…”

“…Chickens are fed rations supplemented with lutein as a source of broiler and yolk pigmentation (21), which results in serum lutein concentrations 15-to 40-fold higher than those in humans (22). In human plasma, the major yellow component associated with TTR was not lutein and was tentatively identified as a yellow pterin derivative, 7,8-dihydropterin-6-carboxaldehyde (23). However, the presence of carotenoid-derived components could not be excluded (20).…”

Lutein associated with a transthyretin indicates carotenoid derivation and novel multiplicity of transthyretin ligands

“…However, extraction of human TTR at acidic pH (~ 2) and elevated temperatures (100 ° C for 5 10 min) can result in the recovery of a highly yellow substance with absorbance maxima at 268, 282 and 430 nm (Fig. 2B), interpreted to constitute a pterin derivative [21]. Mass spectrometric studies of that material have so far been unsuccessful.…”

“…Its absorption spectrum, stability, and chromatographic behaviour are different from those of lutein. The major compound appears to be a pterin-derivative [21], but the presence of additional, carotenoid-derived components should not be excluded. TTR synthesized in liver contributes to the transport of thyroxine to the peripheral tissues, while TTR synthesis in the choroid plexus is considered exclusively to transport thyroxine into the brain [26].…”