Complexity of vitamin E metabolism

Table 1 Overview on metabolites of vitamin E

Metabolite	Methods	Matrix
13’-Hydroxychromanol	GC-MS[139,140]	Human and rat liver microsomes[139,140]
(13’-OH)		Cell culture medium of A549 cells[139]
		HepG2 cells[140,143]
13‘-Carboxychromanol	LC-ESI-MS[136,139]	Human liver microsomes, serum, feces[136,140,142]
(13’-COOH)	HPLC-FD or HPLC-ECD[136,141]	Rat liver microsomes[139,140]
	GC-MS[140]	Mouse feces[136]
		Cell culture medium of A549 cells[139]
		HepG2 cells[140,143]
Carboxydimethyldecyl-hydroxychroman	LC-ESI-MS[136,139,141]	Human feces[136]
(CDMDHC)	HPLC-FD or HPLC-ECD[136,141]	Mouse serum and feces[136]
(11’-COOH)	GC-MS[140]	HepG2 cells[140,143]
Carboxymethyloctyl-hydroxychroman	LC-ESI-MS[136,139,141]	Human and mouse feces[136]
(CDMOHC)	HPLC-FD or HPLC-ECD[136,141]	HepG2 cells[140,143]
(9’-COOH)	GC-MS[140]
Carboxymethylhexyl-hydroxychroman	GC-MS[134,137,140,144]	Human and mouse feces[136]
(CDMHHC)	HPLC-ECD[136,137]	HepG2 cells[120,140,144]
(7’-COOH)	LC-ESI-MS[136]
Carboxymethylbutyl-hydroxychroman	GC-MS[134,137,140,144]	Human serum or plasma, urine and feces[116,134,136,144]
(CMBHC)	HPLC-ECD[136,137]	Mouse liver, serum, urine and feces[136]
(5’-COOH)	LC-ESI-MS[136]	HepG2 cells[120,140,144]
Carboxyethyl-hydroxychroman	LC-ESI-MS[136,139,141]	Human plasma or serum, urine, feces[134-136,140,144,150-152,155,156]
(CEHC)	HPLC-ECD[136,137,149-152]	Rat liver, plasma, bile and urine[141,149,154]
(3’-COOH)	GC-MS[134,137,144,153]	Mouse serum or plasma, urine, feces and liver[134-136,144,151,155,156]
		A549 and HepG2 cells[137,140,141,144]

Table 2 Experimentally validated conjugates of vitamin E metabolites

Metabolite	Conjugate	Organism
LCM	Sulfates	Rats and in vitro[139,141]
ICM	Ether glucuronides	Human and mouse urine[176]
	Sulfates	Human urine[177]
SCM	Glucosides, glutamine	Mouse[156,176]
	Taurine, glycine or glycine glucuronides	Human and mouse urine[176]
	Sulfates	Rats[178]

LCM: Long-chain metabolites; ICM: Intermediate-chain metabolites; SCM: Short-chain metabolites.

Table 3 Genetic polymorphisms of genes encoding for proteins involved in vitamin E homeostasis

Gene	Polymorphism	RefSNP ID	Functional consequence	Ref.
ABCA1	NM_005502.3:c.2828+426A > G	rs4149314	Intron variant	[215]
	NM_005502.3:c.814-1304T > C	rs4149297	Intron variant	[215]
	NM_005502.3:c.161-170G > A	rs11789603	Intron variant	[215]
	NM_005502.3:c.936C > A	rs2274873	Synonymous codon	[215]
	NM_005502.3:c.936C > T
ABCG1	NC_000021.9:g.42167452C > T	rs468320		[215]
APOA5	NM_052968.4:c.-644C > T	rs662799	Upstream variant 2KB	[219]
APOB	NC_000002.12:g.20937665C > T	rs4643493		[215]
	NM_000384.2:c.12541G > A	rs1042031	Intron variant	[215]
			Missense: E4181K
	NC_000002.12:g.21048451A > G	rs1713222		[215]
BET1	NC_000007.14:g.94352727G > A	rs10464587	Intron variant	[215]
CD36	NM_001289911.1:c.-108-13288T > C	rs1527479	Intron variant	[220]
CYP4F2	NM_001082.4:c.1297G > A	rs2108622	Missense: V433M	[217,225]
	NM_001082.4:c.34T > G	rs3093105	Missense: W12G	[225]
IRS1	NC_000002.12:g.226683594A > G	rs1316328		[215]
LIPC	NC_000015.9:g.58688186A > C	rs4238329		[215]
	NM_000236.2:c.89-47937A > G	rs8041525	Intron variant	[215]
	NC_000015.10:g.58394555C > T	rs7164909	Intron variant	[215]
	NC_000015.10:g.58353522T > C	rs8035357	Intron variant	[215]
	NM_000236.2:c.88+49790T > C	rs12591216	Intron variant	[215]
	NM_000236.2:c.89-50891C > A	rs12593880	Intron variant	[215]
NAT2	NC_000008.11:g.18439195T > C	rs4921920		[215]
NPC1L1	NM_013389.2:c.1184C > T	rs62001882	UTR variant 5 prime	[216]
			Missense: A395V
	NM_013389.2:c.1204G > A	rs141973731	UTR variant 5 prime	[216]
			Missense: G402S
	NM_001300967.1:c.1249C > T	rs139659653	UTR variant 5 prime	[216]
			Missense: R417W
	NM_013389.2:c.1300G > A	rs114375162	UTR variant 5 prime	[216]
			Missense: G434R
PNLIP	NM_000936.2:c.930+205T > C	rs2915775	Intron variant	[215]
	NC_000010.11:g.116569152G > T	rs3010494		[215]
SCARB1	NM_001082959.1:c.127-4800C > T	rs11057830	Intron variant	[217]
SEC14L2	NM_033382.2:c.32G > A	rs757660	UTR variant 5 prime	[224]
			Missense: R11K
	NM_016498.4:c.-2240T > C	rs1061660	Upstream variant 2KB, UTR variant 3 prime	[224]
	NM_016498.4:c.-2110G > A	rs1061664	Upstream variant 2KB, UTR variant 3 prime	[224]
SLC10A2	NC_000013.11:g.103037119C > T	rs1571513		[215]
	NC_000013.11:g.103898490C > T	rs9558203		[215]
	NC_000013.11:g.103040492G > A	rs16961116		[215]
	NC_000013.11:g.103444248G > A	rs12874168		[215]
	NC_000013.11:g.103452026G > A	rs2065550		[215]
SREBF2	NM_004599.3:c.2208+3245C > T	rs2839715	Intron variant	[215]
	NM_004599.3:c.1761+160G > A	rs4822062	Intron variant	[215]
TTPA	NM_000370.3:c.421G > A	rs397515524	Intron variant	[222]
			Missense: E141K
	NM_000370.3:c.175C > T	rs397515522	Missense: R59W	[222]
	NM_000370.3:c.-1753G > A	rs12056582	Upstream variant 2KB	[223]
	NM_000370.3:c.-1410A > T	rs6472071	Upstream variant 2KB	[223]
	NM_000370.3:c.-1410A > C
	-345C/T1	rs75371508		[223]
	NM_000370.3:c.-981T > A	rs6994076	Upstream variant 2KB	[223,224]
	NM_000370.3:c.-945G > A	rs34358293	Upstream variant 2KB	[223]
	NM_000370.3:c.-675G > A	rs80169698	Upstream variant 2KB	[223]
	NM_000370.3:c.-440C > T	rs73684515	Upstream variant 2KB	[223]
	-344C/T1	rs74684018		[223]
ZNF664	NM_001204299.1:c.-234+53341T > C	rs7296124	Intron variant	[215]
	NM_152437.2:c.*2065G > A	rs1048497	Intron variant,	[215]
			UTR variant 3 prime
ZPR1	NM_003904.3:c.*724C > G	rs964184	Downstream variant 500B	[217]

¹This variant has been described by Ulatowski et al[223] but was not found in the NCBI dbSNP database (http://www.ncbi.nlm.nih.gov/SNP/).