China
Africa
Explore chapters and articles related to this topic
Aspects of Bilirubin Transport
Published in Karel P. M. Heirwegh, Stanley B. Brown, Bilirubin, 1982
Jules A. T. P. Meuwissen, Karel P.M. Heirwegh
In contrast to common opinion, bilirubin is not truly lipophilic (see Chapter 3, Volume I).2,3It rather shows the properties of an amphipathic compound. The form that occurs in vivo is the dianion.2,3 Formation of complexes with polar lipids such as phosphatidylcholine, presumably results from ionic interaction with the charged head group of the lipids.2 In this form, bilirubin may well become lipid-soluble much in the same way as complexation with albumin conveys water solubility to the pigment. The yellow color of fat and skin, seen when bilirubin becomes displaced from albumin in plasma or when the binding capacity of the latter is exceeded, is not due to dissolution of the pigment in fat, but to binding to extravascular albumin and complex formation with membrane lipids.2,3
Physical Chemistry of Bilirubin: Binding to Macromolecules and Membranes
Published in Karel P. M. Heirwegh, Stanley B. Brown, Bilirubin, 1982
Karel P. M. Heirwegh, Stanley B. Brown
Experimental verification of this reaction scheme and determination of the dimerization constant, KDim, has been accomplished by measuring the ratio of light absorption at 520 and 430 nm in a wide range of bilirubin concentrations (Figure 8).35 As may be seen from the figure, good agreement of observed points with theory is obtained. Since, however, the upper curvature cannot be observed with good precision, it is possible that further oligomerization takes place at high concentrations. On the other hand, this possibility seems remote since formation of aggregates with six or more negative charges on an aggregate of the limited size in question is improbable, except at high ionic strength. The dimerization constant has been determined as a function of temperature and salt concentration, and thermodynamic constants for the process have been calculated.35 At 37°C and ionic strength 0.15 M, the dimerization constant is about 0.25 mM. Bilirubin dianion concentrations in body fluids are below 0.1 µM; the concentration of the dimer is thus extremely low and can usually be disregarded.
Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yuan Gao, Nian-Dong Mao, Hao Che, Li Xu, Renren Bai, Li-Wei Wang, Xiang-Yang Ye, Tian Xie
Intermediate 5g (R = para-OH) possesses at least three reactive centres which could potentially react with intermediate 4. In fact, the designed analog 11g was unable to obtain using the above synthetic route. During the displacement step, double alkylation occurred and compound 16 was isolated. This was explainable that Cs2CO3 was capable to deprotonate both phenolic proton and nitrogen proton of THPO-NH-C(O)- group. The resulting dianion attacked the Br-bearing allylic carbon of 4 to facilitate the double alkylation. The final deprotection of 16 gave the novel dimer derivative 17, which was also subjected to biological testing. It should be noted that compound 19, an analog of 11i with saturated α,β- position of carboximate group, could not be synthesised from 18 and 4 using the above synthetic route. Apparently, the alkylation at the nitrogen of THPO-NH-C(O)- did not proceed as expected. By comparing with the majority of substrates 5 (no matter n is 0 or 1), one could postulate that the conjugated component (C−C double bond or aryl group) directly attaching to THPO-NH-C(O)- was necessitated for N-alkylation (Scheme 3) to generate novel N-alkyl-N-hydroxyl carboximate derivatives of β-elemene.
The interaction between vitamin C and bone health: a narrative review
Published in Expert Review of Precision Medicine and Drug Development, 2018
Alberto Falchetti, Roberta Cosso
At physiological pH, the ascorbate monoanion is the dominant form of vitamin C (99%) followed by ASC and the ascorbate dianion in very low concentrations (0.005%) (Figure 2). At acid pH, ASC is the main molecular form [4–7]. Vitamin C is synthesized from glucose (d-glucuronic acid) in most animals (Figure 3). However, humans and other primates are not able to synthesize vitamin C, because the gene encoding l-gulonolactone oxidase, the last enzyme in ascorbate synthesis, is not functional, probably because of a mutation appeared over 40 million years ago. Standard belief among scientists is that the GULO gene could have been ‘prepared’ to be lost/changed (pseudo-gene) versus other genes, since it produces an enzyme, presumably, not working in other biochemical pathways. However, some questions are still waiting for a clear answer: (1) Since scurvy is fatal, why GULO gene mutation has not been deleted?; (2) Why the consequences of this mutation have not been rapid and fatal?; and (3) Did the mutation occur in a population of mammals with high intakes of vitamin C in the diet? It would have had no consequence in such a population.
Inhibition of Shiga toxin-converting bacteriophage development by novel antioxidant compounds
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Sylwia Bloch, Bożena Nejman-Faleńczyk, Karolina Pierzynowska, Ewa Piotrowska, Alicja Węgrzyn, Christelle Marminon, Zouhair Bouaziz, Pascal Nebois, Joachim Jose, Marc Le Borgne, Luciano Saso, Grzegorz Węgrzyn
Oxazinocarbazole BZ70 was prepared by a Mannich type condensation of benzo[d]thiazol-2-ylmethanamine and formaldehyde with 9-methylcarbazol-4-ol. This latter was obtained by a chemoselective N-alkylation of the commercially available carbazol-4-ol which was achieved by generating the N,O-dianion with NaH in a DMF/THF mixture under argon atmosphere at room temperature and subsequent treatment with methyl iodide45. Dimethoxynin-hydrins (2,2-dihydroxydimethoxyindane-2,3-diones) CM3186B and CM3141B were prepared in a single step from the corresponding commercial substituted indan-1-ones by microwave-assisted selenium oxidation46. Dihydroxyindeno[1,2-b]indole-9,10-dione BZA1547 was prepared by condensation of ninhydrin and 3-(benzylamino)cyclohex-2-en-1-one. 5-Isopropylindeno[1,2-b]indole-9,10-dione derivatives MF148, THN10, THN6C49, MF5, and CM3159B, were synthesized in two steps according to the method previously described47: first, condensation between 3-(isopropylamino)cyclohex-2-en-1-one 247 and the corresponding substituted ninhydrin, then deoxygenation using tetraethylthionylamide (TETA) (Figure 2).