Metabolic Origins and Transport of Vitamin E Biosynthetic Precursors

Abstract

Tocochromanols are organic compounds mostly produced by photosynthetic organisms that exhibit vitamin E activity in animals. They result from the condensation of homogentisate with four different polyprenyl side chains derived all from geranylgeranyl pyrophosphate. The core tocochromanol biosynthesis has been investigated in several photosynthetic organisms and is now well-characterized. In contrast, our current knowledge of the biosynthesis and transport of tocochromanol biosynthetic precursors is much more limited. While tocochromanol synthesis occurs in plastids, converging genetic data in Arabidopsis and soybean demonstrate that the synthesis of the polar precursor homogentisate is located in the cytoplasm. These data implies that tocochromanol synthesis involves several plastidic membrane transporter(s) that remain to be identified. In addition, the metabolic origin of the lipophilic isoprenoid precursor is not fully elucidated. While some genetic data exclusively attribute the synthesis of the prenyl component of tocochromanols to the plastidic methyl erythritol phosphate pathway, multiple lines of evidence provided by feeding experiments and metabolic engineering studies indicate that it might partially originate from the cytoplasmic mevalonate pathway. Although this question is still open, these data demonstrate the existence of membrane transporter(s) capable of importing cytosolic polyprenyl pyrophosphate such as farnesyl pyrophosphate into plastids. Since the availability of both homogentisate and polyprenyl pyrophosphates are currently accepted as major mechanisms controlling the type and amount of tocochromanols produced in plant tissues, we summarized our current knowledge and research gaps concerning the biosynthesis, metabolic origins and transport of tocochromanol biosynthetic precursors in plant cells.

Keywords: Arabidopsis; homogentisate; methyl erythritol phosphate pathway; mevalonate pathway; nutrigenomics; prenyl pyrophosphate; tocochromanols; vitamin E.

FIGURE 1

Plant tocochromanol biosynthetic pathways and chemical structures of prenylquinols and tocochromanols. Whereas all four methylated forms, i.e., α-, β-, γ- and δ-tocochromanol, have been identified in wild-type plants for tocopherols, tocotrienols, and tocomonoenols, only the γ- form of solanesyl-derived tocochromanol PC-8 has been identified in wild-type plants. Its methylated form, methyl PC-8, has been found only in transgenic plants overexpressing VTE4. GGPP, geranylgeranyl pyrophosphate; HGA, homogentisate; HGGT, HGA geranylgeranyl transferase; HST, HGA solanesyl transferase; PC-8, plastochromanol-8; PPP, phytyl pyrophosphate; SAH, S-adenosylhomocystein; SAM, S-adenosylmethionine; SPP, solanesyl pyrophosphate; THGGPP, tetrahydrogeranylgeranyl pyrophosphate; VTE, vitamin E biosynthetic enzyme.

FIGURE 2

Metabolic origins of tocopherol biosynthetic precursors. Model representing the biosynthetic pathways, cellular compartments, and membrane transport proteins involved in the biosynthesis and transport of tocopherol precursors. Several studies suggest that the cytoplasmic MVA pathway might supply prenyl biosynthetic precursors such as farnesyl pyrophosphate for the synthesis of plastidic isoprenoids including carotenoids, plastoquinol-9, chlorophylls, and tocopherols. Compound names in red with an asterisk indicate that the corresponding radiolabeled molecule has been detected following feeding with radiolabeled mevalonate (cytoplasmic MVA pathway). Compound names topped with three red stars and one black star indicate that three quarters of the prenyl side chain of the molecule was radiolabeled following radiolabeled MVA feeding, while one quarter remained unlabeled. Biosynthetic enzymes in blue indicate that they have been demonstrated to be involved in tocopherol metabolism and that their subcellular localization was confirmed. In contrast, enzyme names in black have not been demonstrated involved in tocochromanol metabolism yet. Genetic and biochemical evidence in Arabidopsis and soybean show that HGA synthesis is localized in the cytoplasm. This implies the existence of membrane transport proteins exporting tyrosine and potentially HPP from plastids to the cytoplasm, and of transporter(s) importing HGA back into plastids. None of the transporters symbolized by gray boxes have been identified yet. CoA, coenzyme A; DMAPP, dimethylallyl pyrophosphate; E4P, D-erythrose-4-phosphate; FPP, farnesyl pyrophosphate; G3P, glyceraldehyde-3-phosphate; G4, chlorophyll synthase; GGPP, geranylgeranyl pyrophosphate; GGPPS, geranylgeranyl pyrophosphate synthase; GGR, geranylgeranyl reductase; Glu, L-glutamate; HGA, homogentisic acid; HGO, homogentisic acid dioxygenase; HPP, 4-hydroxyphenylpyruvate; HPPD, 4-hydroxyphenylpyruvate dioxygenase; IPP, isopentenyl pyrophosphate; 4-MA, 4-maleylacetoacetate; MEP, methylerythritol phosphate; MVA, mevalonate; 2-OG, 2-oxoglutarate; PEP, phosphoenolpyruvate; PPP, phytyl pyrophosphate; PYR, pyruvate; TAT, tyrosine aminotransferase; Tyr, tyrosine; VTE, vitamin E biosynthetic enzyme.