Disease relevance of D-fructose-1-phosphate

• Hereditary fructose intolerance (HFI) is an inborn error of metabolism, inherited as an autosomal recessive disorder and caused by a decrease in the activity of fructose-1-phosphate aldolase (aldolase B) in affected individuals [1].
• In addition, a sufficient amount of fructose-1-phosphate rapidly accumulated before the induction of hypoxia, and the linear production of lactate, during hypoxic incubation, indicated that cells synthesized ATP continuously [2].
• Identification of a phosphoenolpyruvate:fructose phosphotransferase system (fructose-1-phosphate forming) in Listeria monocytogenes [3].

High impact information on D-fructose-1-phosphate

• Specific activities of the glycolytic enzymes fructose-1-phosphate aldolase, fructose-1,6-diphophate aldolase, and pyruvate kinase, are higher in rat duodenum and jejunum than in ileum [4].
• Mannose-6-phosphate and fructose-1-phosphate were potent inhibitors of lymphocyte attachment (one-half maximal inhibition at 2-3 mM) [5].
• Under aerobic conditions, both glycolysis (lactate formation) and gluconeogenesis (glucose formation) were carried out in fructose-1-phosphate-loaded cells with the same initial rates, whereas under hypoxic conditions glycolysis was the main metabolic event [2].
• Glutathione S-transferase protein fused either to rat liver or human pancreatic islet glucokinase were able to precipitate glucokinase regulatory protein from liver or hypothalamic extracts in the presence of fructose-6-phosphate, the amount of protein co-precipitated being decreased with fructose-1-phosphate [6].
• Experiments in vitro showed that the synthase phosphatase activity of glycogen-bound type-1 protein phosphatase was increased by physiological concentrations of Glc-6-P (0.1-0.5 mM), but not by 2.5 mM fructose-6-P, fructose-1-P or glucose-1-P [7].

Biological context of D-fructose-1-phosphate

• The system consists of enzyme I, HPr, and a fructose-specific enzyme II complex which generates fructose-1-phosphate as the cytoplasmic product of the PTS-catalyzed vectorial phosphorylation reaction [3].
• Kinetics, also including fructose-1-P, were determined for all these enzymes [8].
• The fru operon consists of three structural genes: fruB(MH), which encodes the enzyme IIIFru-modulator-FPr tridomain fusion protein of the PTS; fruK, which encodes fructose-1-phosphate kinase; and fruA, which encodes enzyme IIFru of the PTS [9].
• Alkyl glycolamido phosphoric esters (P-O-CH2-CO-NH-(CH2)n-CH3) and alkyl monoglycolate phosphoric esters (P-O-CH2-CO-O-(CH2)n-CH3), which are analogs of the aldolase substrate fructose-1-phosphate, were synthesized and use for probing the active site of rabbit muscle aldolase [10].

Anatomical context of D-fructose-1-phosphate

• Fructose (10 mM) or NH4Cl (50 mM) was added to the perfusate, and synthesis of fructose-1-phosphate (F-1-P) and Na- and H-ion transports through the cell membrane were evaluated by magnetic resonance spectroscopy (MRS), 31P-MRS and 23Na-MRS [11].
• Our early 31P n.m.r. studies of compartmentation in suspensions of rat liver cells have been extended by following fructose-1-phosphate peaks, known to be in the cytosol, which gave the same pH as the Pi peak previously assigned to the cytosol [12].
• In contrast, fructose-1-phosphate as well as fructokinase immunoreactivity could be detected in cultured hepatocytes [13].
• Glucose-6-phosphate and fructose-1-phosphate also stimulated osteoblast alkaline phosphatase production, but not to the same extent as M6P [14].
• Fructose-1-phosphate was almost equally as effective at inhibiting uptake into fibroblasts but had no effect on macrophages [15].

Associations of D-fructose-1-phosphate with other chemical compounds

• Sucrose also led to an early rise in the activity of hepatic triokinase, but did not influence ketohexokinase or fructose-1-phosphate aldolase [16].
• FCCP treatment of the liver caused the two peaks to coalesce with the final pH of both the fructose-1-phosphate and inorganic phosphate being the same [17].
• 0. Fructose is phosphorylated in the C1 position by the liver and the resulting fructose-1-phosphate is located in the cytosol [17].
• Glucose-grown cells showed increased activities of the ED enzymes gluconate dehydratase and 2-keto-3-deoxy-gluconate kinase, whereas fructose-grown cells contained higher activities of the key enzymes of a modified EM pathway, ketohexokinase and fructose-1-phosphate kinase [18].
• The hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate is slower than the degradation of D-fructose-1-phosphate [19].

Gene context of D-fructose-1-phosphate

• The inhibition of GCK by GCKR is relieved by the binding of fructose-1-phosphate (F-1-P) to GCKR [20].
• Regulation of glucokinase by a fructose-1-phosphate-sensitive protein in pancreatic islets [21].
• Glucokinase regulatory protein gelled F-actin, and gelation was specifically inhibited by glucokinase and the regulatory protein effectors fructose-1-phosphate (F1P) and fructose-6-phosphate (F6P) [22].
• However, only 6xHis-tagged Cra, and not 6xHis-Cra*, was displaced from the DNA target by the effector, fructose-1-phosphate (F1P), suggesting that the mutant protein is locked in a promoter-binding conformation and is no longer responsive to F1P [23].
• The Km for fructose-1-phosphate (1.7 X 10(-1) M) was higher and the activity with fructose-1,6-biphosphate relative to fructose-1-phosphate (Vmax FBP/Vmax F-1-P = 0.038) was much lower than for either liver or muscle aldolase [24].

Analytical, diagnostic and therapeutic context of D-fructose-1-phosphate

• As is the case in animal experiments, in human lenses, too, the first step in the phosphorylation to fructose-1-phosphate via the enzyme ketohexokinase [25].

References