A major difficulty is revealed by comparison of the small net fluxes for the large, essential neutral amino acids and the large provision of these amino acids required for transamination to convert α-ketoglutarate into glutamate (see Figs. 16 and 17). For this requirement to be satisfied by influx across the blood–brain barrier of leucine, isoleucine and valine, their combined net influx would need to be > 100 nmol min−1 g−1 (see Sect. 5.5.1). For a cerebral blood flow of 0.57 mL min−1 g−1 (see e.g. Sect. 5.3) that would correspond to an A − V difference > 175 µM. Given that the total of the arterial plasma concentrations for these amino acids is only 392 µM (see Table 3), this A − V difference and hence net rate of transport should have been well above the “noise” in all of the studies, even that in rats (see Table 4).