Formation in vivo of glycogen by certain intermediates of the lactate-propanediol pathway.

It has been observed by Miller and Olson (1) in experiments with heart muscle slices with the use of pyruvate and lactate as substrates in an anaerobic system that 0.1 M fluoride completely inhibited the utilization of pyruvate while lactate utilization was unimpaired. Since fluoride inhibits the enolase reaction in the Embden-Meyerhof glycolytic pathway, it was postulated that lactate could be metabolized by an alternative pathway not involving its conversion to pyruvate. Miller et al. (2) suggested that the alternative lactate pathway might involve lactaldehyde, acetol, and 1,2-propanediol either in the free or phosphorylated forms. Huggins and Miller (3) and Sandman and Miller (4) have demonstrated the conversion of 1,2-propanediol to acetol as well as the conversion of acetol to 1,2-propanediol under anaerobic conditions using yeast cells. Lactaldehyde was also converted to 1,2-propanediol, lactate, and acetol. Yeast cells appear to utilize the nonphosphorylated rather than the phosphorylated forms of these intermediates (4). Sellinger and Miller (5, 6) have reported that rat liver and kidney homogenates convert acetol to acetol phosphate in the presence of ATP, and that acetol phosphate can be reduced to 1,2-propanediol l-phosphate in the presence of DPNH by a specific dehydrogenase. Huang and Miller (7) have suggested that the naturally occurring methylpentose, n-fucose, could be synthesized from n-lactaldehyde and dihydroxyacetone phosphate. In the presence of aldolase these two compounds form 6-deoxy-n-sorbose l-phosphate which in the presence of the appropriate epimerase and isomerase could form n-fucose l-phosphate. Hanzlik et al. (8) have shown that 1,2-propanediol is glycogenie in the fasted rat. Rudney (9) fed male rats nn-propanediol labeled with 04 in the C-l position and determined the label in the glucose isolated from the liver glycogen. The relatively high activity of the 3,4-carbons of the glucose suggested that at least some of the propanediol was converted directly to lactate. If acetol and lactaldehyde are intermediates in the conversion of 1,2-propanediol to lactate, they would be expected to be glycogenic since lactate is readily converted to glycogen. It was, therefore, decided to investigate the glycogenic potency of these intermediates. The formation of glycogen from n-fucose was also studied. A preliminary report of this work has been presented (10).