ChemInform Abstract: Synthesis and Squalene Synthetase Inhibitory Activity of Tripotassium 1-Methyl-1-((N-benzyl-N-farnesyl)aminoethylphosphinato) ethylphosphonate (I) as a Tethered Analog of N-Benzyl-N-farnesylamine - Inorganic Pyrophosphate Ion Pair.

1. In order to assess the relative importance of possible pathogenetic factors in the formation of calcium-containing renal stones, a group of 18 patients (12 men, six women) with active, recurrent stone disease were compared with 16 age-matched control subjects (10 men, six women) given an identical diet. 2. Fifteen (83%) of the patients showed at least one, eight (44%) showed two, and one (6%) patient showed three abnormalities that might predispose to stone formation. 3. Increased urinary calcium excretion was the most common abnormality (11 patients, 61%), particularly in the women (83%). 4. A diminished excretion of inhibitors of crystal formation of calcium phosphate was the next most common abnormality, which occurred in eight patients (44%), all of whom were men. It was largely attributable to a diminished excretion of inorganic pyrophosphate (PPi). The PPi/orthophosphate ratios were also lower in the stone-formers. Significant differences in residual inhibitory activity after enzymatic removal of PPi between control subjects and stone-formers could not be found in 24 h urine samples but were present during certain times of the day. Pyrophosphate showed a higher inhibitory activity in urine than in control solutions, this enhancement being absent in stone-formers. 5. Nine (50%) of the patients, but only one of the control subjects, produced crystal aggregates greater than 50 μm in diameter after an oral load of oxalate.

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Crystal structures of plant inorganic pyrophosphatase, an enzyme with a moonlighting autoproteolytic activity

Biochemical Journal ◽

10.1042/bcj20190427 ◽

2019 ◽

Vol 476 (16) ◽

pp. 2297-2319 ◽

Cited By ~ 3

Author(s):

Marta Grzechowiak ◽

Milosz Ruszkowski ◽

Joanna Sliwiak ◽

Kamil Szpotkowski ◽

Michal Sikorski ◽

...

Keyword(s):

Site Directed Mutagenesis ◽

Size Exclusion ◽

Inorganic Pyrophosphatase ◽

Prolonged Storage ◽

Mitochondrial Targeting ◽

Cleavage Rate ◽

Inorganic Pyrophosphate ◽

Putative Signal Peptide ◽

Targeting Peptide

Abstract Inorganic pyrophosphatases (PPases, EC 3.6.1.1), which hydrolyze inorganic pyrophosphate to phosphate in the presence of divalent metal cations, play a key role in maintaining phosphorus homeostasis in cells. DNA coding inorganic pyrophosphatases from Arabidopsis thaliana (AtPPA1) and Medicago truncatula (MtPPA1) were cloned into a bacterial expression vector and the proteins were produced in Escherichia coli cells and crystallized. In terms of their subunit fold, AtPPA1 and MtPPA1 are reminiscent of other members of Family I soluble pyrophosphatases from bacteria and yeast. Like their bacterial orthologs, both plant PPases form hexamers, as confirmed in solution by multi-angle light scattering and size-exclusion chromatography. This is in contrast with the fungal counterparts, which are dimeric. Unexpectedly, the crystallized AtPPA1 and MtPPA1 proteins lack ∼30 amino acid residues at their N-termini, as independently confirmed by chemical sequencing. In vitro, self-cleavage of the recombinant proteins is observed after prolonged storage or during crystallization. The cleaved fragment corresponds to a putative signal peptide of mitochondrial targeting, with a predicted cleavage site at Val31–Ala32. Site-directed mutagenesis shows that mutations of the key active site Asp residues dramatically reduce the cleavage rate, which suggests a moonlighting proteolytic activity. Moreover, the discovery of autoproteolytic cleavage of a mitochondrial targeting peptide would change our perception of this signaling process.

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Systematic procedure for the determination of the nature of the solutes prior to the selection of the mobile phase parameters for optimization of reversed-phase ion-pair chromatographic separations

Journal of Chromatography A ◽

10.1016/s0021-9673(01)84371-5 ◽

1989 ◽

Vol 478 (1) ◽

pp. 21-38 ◽

Cited By ~ 1

Author(s):

G Low

Keyword(s):

Mobile Phase ◽

Reversed Phase ◽

Ion Pair ◽

Chromatographic Separations ◽

Systematic Procedure ◽

Selection Of

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Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000652 ◽

2020 ◽

pp. 1-9

Author(s):

Pınar Ercan ◽

Sedef Nehir El

Keyword(s):

Inhibitory Activity ◽

Digestive Enzymes ◽

Positive Control ◽

Anthocyanin Content ◽

Inhibitory Effects ◽

Total Anthocyanin ◽

Total Anthocyanin Content ◽

Before And After ◽

Red Grape

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.

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