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.