Changes in Activity and Molecular Properties of Fructose 1,6-Bisphosphatase During Fasting and Refeeding

Abstract

During prolonged starvation, fructose 1,6-bisphosphatase (EC 3.1.3.11) activity in rabbit liver and kidney shows a transient decrease during the first 36 hr., before rising at 96 hr to levels severalfold higher than those found in the livers of fed animals. Proteolytic activity appears in the 105,000 X g supernatant fraction within several hours of starvation, and continues to increase during the entire 96-hr period. On refeeding, the activities return to nearly the control levels within 24 hr. The catalytic properties of fructose 1,6-bisphosphatase isolated from the livers of fasted rabbits are similar to those of the enzyme from fed animals, but its structure is modified, since it no longer contains the single tryptophan residue located near the NH2-terminus in the native enzyme. Thus this tryptophan residue is not required for the neutral pH optimum. The structural changes and the transient decrease in activity may be related to the observed increase in "free" proteolytic activity.

Hormonal effects on structure and catalytic properties of fructose 1,6-bisphosphatase.

“…In addition, these enzymes always contained traces of a lighter subunit, with molecular weight of 29,000, which was not detected in the enzyme purified from the control animals. These changes were similar to those reported earlier for the enzyme purified from fasted animals (5), (see also Table 2) or animals exposed to cold (2,17). We have previously presented evidence that the tryptophan residue is located in the NH2-terminal portion of the molecule (21) but the precise nature of the difference in the molecular structure cannot be determined, because in both forms of the enzyme the NH2-terminus appears to be masked ( Table 2).…”

“…Certain gluconeogenic conditions (e.g., fasting or prolonged starvation) are known to be associated with the breakdown of protein in peripheral tissues (1) as well as increased proteolytic activity in liver (2). Associated with these generally catabolic conditions are large increases in the activities of hepatic gluconeogenic enzymes (3)(4)(5). These effects probably involve the intervention of gluconeogenic hormones, since similar increases in lysosomal activity and gluconeogenic enzymes have been reported following the administration of glucagon and glucocorticoids (6)(7)(8)(9)(10)(11)(12).…”

Changes during fasting in the activity of a specific lysosomal proteinase, fructose-1,6-bisphosphatase converting enzyme.

“…The change is particularly striking in the case of CE-IT, the activity of which is increased by more than 5-fold compared with increases of less than 2-fold for the other converting enzymes and for marker lysosomal enzymes such as cathepsins B and C and LAP. Thus, the increase in activity of CE-II cannot be attributed to the general increase in number and activity of rabbit liver lysosomes that we observed earlier (9,16). Even more noteworthy is the change in the activity in the membrane-bound converting enzyme, which increased by more than 10-fold.…”

Regulation of Fructose 1,6-Bisphosphatase by Histidine under Gluconeogenic Conditions

“…Adult female brown rabbits, weighing 2.5-2.8 kg, were obtained from the local Italian market and maintained on a stock diet or fasted as reported (6). Animals were killed by cervical dislocation; the livers were removed immediately and cooled in crushed ice.…”

“…The requirement for histidine becomes more pronounced under gluconeogenic conditions, because of a structural modification of Fru-P2ase in vivo whereby a small tryptophan-containing peptide is removed from the NH2 terminus (6). Thus the primary event leading to the regulation of Fru-P2ase in gluconeogenesis may be the observed increase in lysosomes and lysosomal proteolytic activity (6,7); this would result in a general degradation of proteins and release of free amino acids, including histidine, and the concurrent modification of Fru-P2ase would result in an enhanced response to this amino acid. Analysis of histidine levels in the livers of fed, fasted, and refed rabbits confirm that these levels change in a manner consistent with the requirements for gluconeogenesis.…”