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Molecules (Basel, Switzerland) Dec 2019Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its... (Review)
Review
Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease the bioavailability of important minerals under certain circumstances. However, during the past 30 years, researchers have identified many important health benefits of phytate. Thus, 150 years have elapsed since the discovery of phytate to the first descriptions of its beneficial effects. This long delay may be due to the difficulty in determining phytate in biological media, and because phytate dephosphorylation generates many derivatives (InsPs) that also have important biological functions. This paper describes the role of InsP6 in blocking the development of pathological calcifications. Thus, in vitro studies have shown that InsP6 and its hydrolysates (InsPs), as well as pyrophosphate, bisphosphonates, and other polyphosphates, have high capacity to inhibit calcium salt crystallization. Oral or topical administration of phytate in vivo significantly decreases the development of pathological calcifications, although the details of the underlying mechanism are uncertain. Moreover, oral or topical administration of InsP6 also leads to increased urinary excretion of mixtures of different InsPs; in the absence of InsP6 administration, only InsP2 occurs at detectable levels in urine.
Topics: Animals; Calcinosis; Calcium; Crystallization; Humans; Inositol Phosphates; Phytic Acid
PubMed: 31817119
DOI: 10.3390/molecules24244434 -
Molecules (Basel, Switzerland) Apr 2020Inositol, or myo-inositol, and associated analog molecules, including myo-inositol hexakisphosphate, are known to possess beneficial biomedical properties and are now... (Review)
Review
Inositol, or myo-inositol, and associated analog molecules, including myo-inositol hexakisphosphate, are known to possess beneficial biomedical properties and are now being widely studied. The impact of these compounds in improving diabetic indices is significant, especially in light of the high cost of treating diabetes mellitus and associated disorders globally. It is theorized that, within ten years, the global population of people with the disease will reach 578 million individuals, with the cost of care projected to be approximately 2.5 trillion dollars. Natural alternatives to pharmaceuticals are being sought, and this has led to studies involving inositol, and myo-inositol-hexakisphosphate, also referred to as IP6. It has been reported that IP6 can improve diabetic indices and regulate the activities of some metabolic enzymes involved in lipid and carbohydrate metabolism. Current research activities have been focusing on the mechanisms of action of inositol and IP6 in the amelioration of the indices of diabetes mellitus. We demonstrated that an IP6 and inositol combination supplement may regulate insulin secretion, modulate serum leptin concentrations, food intake, and associated weight gain, which may be beneficial in both prediabetic and diabetic states. The supplement attenuates vascular damage by reducing red cell distribution width. Serum HDL is increased while serum triglycerides tend to decrease with consumption of the combination supplement, perhaps due to the modulation of lipogenesis involving reduced serum lipase activity. We also noted increased fecal lipid output following combination supplement consumption. Importantly, liver function was found to be preserved. Concurrently, serum reactive oxygen species production was reduced, indicating that inositol and IP6 supplement consumption may reduce free radical damage to tissues and organs as well as serum lipids and blood glucose by preserving liver function. This review provides an overview of the findings associated with inositol and IP6 supplementation in the effective treatment of diabetes with a view to proposing the potential mechanisms of action.
Topics: Animals; Biomarkers; Blood Cell Count; Carbohydrate Metabolism; Diabetes Mellitus; Dietary Supplements; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Inositol; Intestines; Leptin; Lipid Metabolism; Metabolic Networks and Pathways; Phytic Acid; Treatment Outcome
PubMed: 32290029
DOI: 10.3390/molecules25071720 -
MSphere Jun 2019Inositol-6-phosphate, also known as phytic acid, is a phosphorus source that plays several important roles in the phosphorus cycle and in cell metabolism. The known...
Inositol-6-phosphate, also known as phytic acid, is a phosphorus source that plays several important roles in the phosphorus cycle and in cell metabolism. The known characterized enzymes responsible for its degradation, the phytases, are mostly derived from cultured individual microorganisms. The catalytic signatures of phytases are restricted to the molecular domains of four protein superfamilies: histidine phosphatases, protein tyrosine phosphatases, the purple acid phosphatases and the β-propeller phosphatases. During function-based screening of previously generated forest soil metagenomic libraries for clones conferring phytase activity, two positive clones harboring the plasmids pLP05 and pLP12 were detected. Analysis of the insert sequences revealed the absence of classic phosphatase/phytase signatures of the proteins deduced from the putative genes, but the genes (pLP05) and (pLP12) encoded putative metallo-β-lactamases (MBLs). Several MBL representatives are promiscuous proteins with phosphoesterase activity, but phytase activity was previously not reported. Both and were subcloned, expressed, and analyzed. Mblp01 and Mblp02 are members of the lactamase B2 family. Protein modeling showed that the closest structural homologue of both proteins was ZipD of Mblp01 and Mblp02 showed activity toward the majority of the tested phosphorylated substrates, including phytate. The maximal enzyme activities were recorded for Mblp01 at 50°C under acidic conditions and for Mblp02 at 35°C and a neutral pH. In the presence of Cu or SDS, the activities of Mblp01 and Mblp02 were strongly inhibited. Analyses of the minimal inhibitory concentrations of several β-lactam antibiotics revealed that recombinant cells carrying or showed reduced sensitivity toward β-lactam antibiotics. Phytic acid is a phosphorus storage molecule in many plant tissues, a source of phosphorus alternative to phosphate rocks, but it can also be a problematic antinutrient. In comparison to other phosphorus sources, phytic acid exhibits reduced bioavailability. Additionally, it influences functions of secondary messengers and acts as antioxidant in tumor growth prevention. The enzymatic capability to process phytate has been reported for a limited number of protein families. This might be due to the almost exclusive use of proteins derived from individual microorganisms to analyze phytase activity. With such a restriction, the study of the complexity and diversity of the phytases remains incomplete. By using metagenome-derived samples, this study demonstrates the existence of phytase activity in one of the most promiscuous superfamilies, the metallo-β-lactamases. Our results increase the general knowledge on phytase diversity in environmental samples and could provide new avenues for the study and engineering of new biocatalysts.
Topics: 6-Phytase; Catalytic Domain; Escherichia coli; Metagenomics; Phytic Acid; Soil Microbiology; beta-Lactamases
PubMed: 31217298
DOI: 10.1128/mSphere.00167-19 -
Plant Physiology Sep 2000Phytic acid (myo-inositol-1, 2, 3, 4, 5, 6-hexakisphosphate or Ins P(6)) typically represents approximately 75% to 80% of maize (Zea mays) seed total P. Here we describe...
Phytic acid (myo-inositol-1, 2, 3, 4, 5, 6-hexakisphosphate or Ins P(6)) typically represents approximately 75% to 80% of maize (Zea mays) seed total P. Here we describe the origin, inheritance, and seed phenotype of two non-lethal maize low phytic acid mutants, lpa1-1 and lpa2-1. The loci map to two sites on chromosome 1S. Seed phytic acid P is reduced in these mutants by 50% to 66% but seed total P is unaltered. The decrease in phytic acid P in mature lpa1-1 seeds is accompanied by a corresponding increase in inorganic phosphate (P(i)). In mature lpa2-1 seed it is accompanied by increases in P(i) and at least three other myo-inositol (Ins) phosphates (and/or their respective enantiomers): D-Ins(1,2,4,5,6) P(5); D-Ins (1,4,5,6) P(4); and D-Ins(1,2,6) P(3). In both cases the sum of seed P(i) and Ins phosphates (including phytic acid) is constant and similar to that observed in normal seeds. In both mutants P chemistry appears to be perturbed throughout seed development. Homozygosity for either mutant results in a seed dry weight loss, ranging from 4% to 23%. These results indicate that phytic acid metabolism during seed development is not solely responsible for P homeostasis and indicate that the phytic acid concentration typical of a normal maize seed is not essential to seed function.
Topics: Electrophoresis; Inositol Phosphates; Magnetic Resonance Spectroscopy; Mutation; Phenotype; Phosphates; Physical Chromosome Mapping; Phytic Acid; Seeds; Stereoisomerism; Zea mays
PubMed: 10982449
DOI: 10.1104/pp.124.1.355 -
Poultry Science Jan 2020Cobb 400, male broilers (n = 4,752) were housed in 12 pens/diet and 33 birds/pen. There were 3 levels of phytate P (0.24, 0.345, or 0.45%) and 4 phytase doses (0, 500,...
Increasing dietary phytate has a significant anti-nutrient effect on apparent ileal amino acid digestibility and digestible amino acid intake requiring increasing doses of phytase as evidenced by prediction equations in broilers.
Cobb 400, male broilers (n = 4,752) were housed in 12 pens/diet and 33 birds/pen. There were 3 levels of phytate P (0.24, 0.345, or 0.45%) and 4 phytase doses (0, 500, 1,000 or 2,000 phytase units (FTU)/kg) to evaluate the influence of phytate and phytase dose on apparent ileal digestibility (AID) and digestible nutrient intake. Diets were formulated with reduced Ca (0.22%), available P (0.20%), energy (80 to 120 kcal/kg) and amino acids (1 to 5%). On day 21, digesta was collected from 8 birds/pen. Prediction equations determined the linear or non-linear influence of phytate P, log phytase dose, and the interaction. The AID of amino acids, Ca or P and digestible amino acid or Ca intake were influenced by linear or non-linear phytate P × log phytase dose (P < 0.0001). Increasing the dietary phytate P from 0.24 to 0.345 or 0.45% was predicted to reduce the AID of amino acids in a non-linear manner by an average of 6 to 7 percentage points, respectively. This corresponded to a non-linear decrease in digestible amino acid intake of an average of 80 to 90 mg/D. The negative effect of increasing dietary phytate P from 0.24 to 0.45% on AID was greatest for cysteine (-14 percentage points), aspartic acid or glycine (-9 percentage points) and lowest for methionine, tryptophan, serine, or glutamic acid (-5 percentage points). The predicted digestible intake of lysine (-120 mg/D), aspartic acid (-180 mg/D), or glutamic acid (-290 mg/D) were reduced in birds fed diets containing 0.345% vs. 0.24% phytate P. Phytase supplementation was predicted to increase the AID of amino acids, Ca, or P in a non-linear-log or log-linear manner at all levels of phytate P, with the greatest response at higher doses of phytase in diets containing 0.345 or 0.45% phytate P. The effect of phytase on digestible nutrient intake was less clear. Prediction equations can be useful to determine the influence of phytase and phytate P on AID and digestible nutrient intake in broilers.
Topics: 6-Phytase; Amino Acids; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Calcium; Chickens; Diet; Digestion; Gastrointestinal Tract; Male; Phosphorus; Phytic Acid
PubMed: 32416813
DOI: 10.3382/ps/pez489 -
The American Journal of Clinical... Jun 2005
Topics: Calcium; Calcium, Dietary; Child; Humans; Intestinal Absorption; Isotope Labeling; Phytic Acid; Rickets; Vitamin D
PubMed: 15941902
DOI: 10.1093/ajcn/81.6.1451 -
Open Biology Nov 2015Here are comments on the recent paper on the determination of inositol hexaphosphate (IP6) in human plasma and on its efficacy.
Here are comments on the recent paper on the determination of inositol hexaphosphate (IP6) in human plasma and on its efficacy.
Topics: Animals; Humans; Inositol Phosphates; Phytic Acid
PubMed: 26581571
DOI: 10.1098/rsob.150048 -
Poultry Science Feb 2023The objective of this study was to evaluate a precision-fed rooster assay that is suitable for determination of phytic acid (myo-inositol 1,2,3,4,5,6-hexakis; InsP)...
The objective of this study was to evaluate a precision-fed rooster assay that is suitable for determination of phytic acid (myo-inositol 1,2,3,4,5,6-hexakis; InsP) disappearance in plant-based feed ingredients. A 48-h precision-fed rooster assay was used to measure InsP disappearance using conventional White Leghorn roosters. A minimum of 4 individually-caged roosters per treatment were fasted for 26 h prior to crop intubation with 15 to 30 g of sample, and excreta were quantitatively collected for 48 h. Soybean meal, soybean hulls, canola meal, conventional distillers dried grains with solubles (DDGS), palm kernel meal (PKM), and wheat bran were evaluated in Experiment 1, whereas wheat middlings (WM) and rice bran (RB) were evaluated without and with 1,000 and 1,800 U/kg phytase in Experiment 2. Data from Experiment 1 were subjected to a one-way ANOVA for a completely randomized design, while data from Experiment 2 were subjected to two-way ANOVA for a 2 × 3 factorial arrangement of treatments. In Experiment 1, InsP disappearance ranged from 3 to 95% among all ingredients. The InsP disappearance for conventional DDGS (95%) was the highest (P < 0.05), wheat bran and soybean hulls were intermediate (47-48%), PKM was low (24%), and soybean meal and canola meal were very low (3-5%). In Experiment 2, there was a significant ingredient × phytase interaction (P < 0.05). Phytase inclusion at both 1,000 and 1,800 U/kg resulted in a significant improvement (P < 0.05) in InsP disappearance for RB; however, only the addition of 1,800 U/kg resulted in an increase in InsP disappearance for WM. The addition of 1,800 U/kg phytase increased the InsP disappearance from 58 to 74% for WM and from 26 to 53% for RB. These results suggest the precision-fed rooster assay can be used to evaluate phytic acid disappearance in plant-based feed ingredients and the assay was able to detect a significant effect of 1,800 U/kg of exogenous phytase on phytic acid disappearance for WM and RB.
Topics: Animals; Male; Diet; Chickens; Digestion; Phytic Acid; 6-Phytase; Glycine max; Dietary Fiber; Animal Feed; Animal Nutritional Physiological Phenomena
PubMed: 36493548
DOI: 10.1016/j.psj.2022.102356 -
Structure (London, England : 1993) Oct 2021Protein N-terminal acetylation is predominantly a ribosome-associated modification, with NatA-E serving as the major enzymes. NatC is the most unusual of these enzymes,...
Protein N-terminal acetylation is predominantly a ribosome-associated modification, with NatA-E serving as the major enzymes. NatC is the most unusual of these enzymes, containing one Naa30 catalytic subunit and two auxiliary subunits, Naa35 and Naa38; and substrate selectivity profile that overlaps with NatE. Here, we report the cryoelectron microscopy structure of S. pombe NatC with a NatE/C-type bisubstrate analog and inositol hexaphosphate (IP), and associated biochemistry studies. We find that the presence of three subunits is a prerequisite for normal NatC acetylation activity in yeast and that IP binds tightly to NatC to stabilize the complex. We also describe the molecular basis for IP-mediated NatC complex stabilization and the overlapping yet distinct substrate profiles of NatC and NatE.
Topics: Acetylation; Binding Sites; Phytic Acid; Protein Binding; Protein Multimerization; Schizosaccharomyces; Schizosaccharomyces pombe Proteins
PubMed: 34019809
DOI: 10.1016/j.str.2021.05.003 -
Journal of Animal Science Jul 2022Myo-inositol is a breakdown product of phytate produced in the gut through the action of phytase. Although the effect of phytase-released phosphorus (P) on growth...
Effects of supplemental myo-inositol on growth performance and apparent total tract digestibility of weanling piglets fed reduced protein high-phytate diets and intestinal epithelial cell proliferation and function.
Myo-inositol is a breakdown product of phytate produced in the gut through the action of phytase. Although the effect of phytase-released phosphorus (P) on growth performance of animals has been well characterized, there is still little understanding of the effect of myo-inositol. The first objective of this study was to determine the effects of added myo-inositol to a phytate-rich low-protein diet on growth performance and apparent total tract digestibility (ATTD) in growing piglets. The second objective was to determine whether myo-inositol could directly affect intestinal epithelial cell proliferation and function for which we used intestinal porcine epithelial cells (IPEC-J2). A total of 128 weanling piglets were allotted to four dietary treatments consisting of eight replicates per treatment and four piglets per replicate in a randomized complete block design for 4 wk. The four experimental diets comprised the positive control [PC; 20% crude protein (CP)], negative control (NC; 17% CP), negative control plus 2.0g/kg myo-inositol (NC+INO; 17% CP), and negative control plus 3000FTU/kg phytase (NC+PHY; 17% CP). Average daily feed intake (ADFI), average daily gain (ADG), and gain-feed ratio (G: F) were recorded. Phytase supplementation in the protein-deficient NC diet increased the G:F ratio (P < 0.05) without myo-inositol effects on growth performance. Phosphorus digestibility in the phytase-supplemented group increased compared to the PC, NC, and NC+INO groups, whereas plasma myo-inositol concentration was significantly higher (P < 0.05) in the NC+INO group. Due to the lack of myo-inositol effect on growth performance, an additional in vitro study was conducted to determine the direct effect of myo-inositol on the intestinal epithelium that might not be reflected in growth performance. Myo-inositol increased the mRNA abundance of selected nutrient transporters in a concentration-dependent manner (P < 0.05). Myo-inositol also enhanced barrier integrity in the IPEC-J2 monolayer by increasing the transepithelial electrical resistance (TEER) with reduced paracellular permeability of FITC-dextran (P < 0.05). In conclusion, despite the lack of myo-inositol effect on animal performance, the in vitro data indicate that myo-inositol may directly regulate gut barrier integrity. Addition of myo-inositol to pig diets at levels that enhance intestinal epithelial cell function may result in effects on growth performance and gut health of pigs.
Topics: 6-Phytase; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Cell Proliferation; Diet; Diet, Protein-Restricted; Dietary Supplements; Digestion; Inositol; Phosphorus; Phytic Acid; Swine
PubMed: 35589552
DOI: 10.1093/jas/skac187