Tetrose metabolism. 2. The utilization of tetroses and tetritols by rat tissues

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Abstract
The metabolism of a number of specifically C14-labelled tetroses and tetritols has been studied in the intact rat and in rat-liver slices aerobically incubated. In the intact fasted rat, intraperitoneally administered specifically labelled L-erythrulose is fairly extensively metabolized. Average recoveries of C14 during 3 hr. after the injection were, from the I-C14-labelled compound, 25% in respiratory CO2,3.8% in liver glycogen and 15% in urinary excretion. From the 4-C14-labelled compound the corresponding values were 15.5, 4.8 and 20% respectively. The time course of C14O2 elimination in respiration during the 3 hr. experiments differs for the 2 labelled erythruloses. The glucose of the liver glycogen is differently labelled according to the labelled erythrulose given. With [1-C14]erythrulose 62% of total labelling appeared in C-l+C-2-C-3 of glucose and 27% in C-6. With the 4-C14 -labelled compound a more symmetrical labelling (48 and 45% respectively) was observed in these groups of glucose carbon atoms. Minor amounts (about 10%) were found in C-4+C-5 of glucose. Rat-liver slices also metabolize L-erythrulose, an average of only 13% of the substrate being recovered after incubation for 90 min. Of the remainder, C14O2 formation accounted for 12% of 1-C14 and 5% of 4-C14 of the original erythrulose activity, glucose contained 4.3 and 2.7% respectively, and reduction of part of the erythrulose to tetritol accounted for 12% with either labelled erythrulose. Degradation of the glucose produced by rat liver slices incubated with labelled L-erythrulose showed that the pattern of labelling was essentially similar to that in the whole animal, except for a slight preponderance in C-6 over C-1+C-2+C-3 when [4-C] erythrulose was the substrate. More elaborate degradations were done on the glucose produced by liver slices, and showed that with both labelled ketotetroses nearly all the labelling reported for C-1+C-2+C-3 of glucose is in fact in C-1. The urinary metabolites included about 4% of the dose of C14 as tetritols, threitol being the only detectable substance in this fraction of the excretion products; no erythritol was formed. The nature of the tetritols produced in the slice experiments was not studied, but it is probable that in both instances reduction of L-erythrulose to L-threitol had occurred by means of the diphosphopyridine nucleotide-xylitol (D-xylulose) dehydrogenase of mammalian liver. D-[4-C14]Erythrose is metabolized by rat liver slices, yielding in 90 min. 1% of the labelling as C14O2 and about 2.5% as glucose. Here the labelling of the glucose carbon atoms is predominantly (73%) in C-6 and 22% in C-1+C-2+C-3 with only 5% in C-4+C-5. The metabolism of some labelled tetritols in rat-liver slices has been studied. [1-C14 ]Erythritol, electrophoretically separated from the product of catalytic hydrogenation of L-[4-C14] erythrulose, was not appreciably converted into C4c2 or [C14]-glucose. Various preparations of L-threitols, produced from L-[1-C14]- and L-[4-C14]-erythrulose, were metabolized, though to a less extent than L-erythrulose itself. It is suggested that preliminary enzymic oxidation to L-erythrulose would be consistent with the extent of L-threitol metabolism observed. Possible pathways of tetrose metabolism are discussed. It was shown in connexion with the incorporation into glucose that the 2 CH2-OH groups of free dihydroxyacetone behave, as expected, identically in enzymic reactions, unlike the corresponding groups in glycerol.