Alpha-tocopherol transfer protein does not regulate cellular uptake and distribution of tocopherols and tocotrienols

Alpha-tocopherol transfer protein (alpha-TTP) does not regulate the cellular uptake and intracellular localisation of alpha-tocopherol, gamma-tocopherol, alpha-tocotrienol and gamma-tocotrienol, as demonstrated in a recently-published study

A group of researchers from Institute of Biological Chemistry and Nutrition, Germany, has verified that cellular uptake and intracellular localisation of tocopherols and tocotrienols were not affected by the presence of alpha-TTP. This is contrary to the common belief about alpha-TTP.

In the study, two different hepatic cells (HepG2) were cultured — with and without stable expression of alpha-TTP — to investigate the role of alpha-TTP in the intracellular distribution of alpha-tocopherol, gamma-tocopherol, alpha-tocotrienol and gamma-tocotrienol.

These four isoforms of vitamin E were chosen to evaluate the importance of the methylation pattern and side-chain saturation for intracellular trafficking of Vitamin E. (Note: tocopherol is commonly known as the saturated of vitamin E, whereas tocotrienol, the unsaturated vitamin E).

The cellular uptake of tocotrienol is higher than those corresponding tocopherol isoforms and this is inferred from its unsaturated side chain that allows tocotrienol to have a higher inter-membrane mobility.

The presence and absence of alpha-TTP, on the other hand, does not affect the cellular uptake.

In regard to intracellular distribution, for both HepG2 cell lines (with and without alpha-TTP), all four isoforms in this study accumulate mainly in these three organelles, namely endoplasmic reticulum, plasma membrane and lysosomes.

This demonstrates that alpha-TTP, methylation pattern or side-chain saturation do not regulate/interfere with intracellular distribution of the Vitamin E isoforms.

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In addition, only alpha-tocopherol accumulates in the mitochondria of both HepG2 cell lines, irrespective of alpha-TTP expression.

Hence, suggesting that alpha-TTP is not involved in distribution of alpha-tocopherol to mitochondria.

The researchers concluded that alpha-TTP, despite its preferential binding to alpha-tocopherol, does not determine or regulate the uptake and intracellular localisation of Vitamin E isoforms. Instead, there are other processes involved in the distribution of vitamin E within liver cells that warrant future study.

“Historically, the high affinity and binding of alpha-TTP with alpha-tocopherol was thought to favour alpha-tocopherol and disadvantage the other forms of tocopherol and tocotrienol in the transport and absorption of vitamin E into the plasma."

"This new finding gives a different view on alpha-TTP’s role that the higher affinity to alpha-TTP doesn’t equate to better cellular uptake and intracellular distribution of tocopherols and tocotrienols,” says Diyanah Roslan, Nutritionist at ExcelVite.

“This reminds us about another study conducted on alpha-TTP-knockout mice at the Ohio State University Medical Centre. The study reveals that tocotrienols are transported to and accumulated in vital organs, even without the presence of alpha-TTP. Hence, there is a secondary transport mechanism for tocotrienols or vitamin E,” added Diyanah Roslan.

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