Hydrophilic conjugates

Some metabolic conjugative processes result in the production of lipophilic derivatives that are not readily eliminated. While their physical properties are different from the classical hydrophilic conjugates, the mechanism of formation clearly defines them as conjugates (i.e., they are formed as the result of a union of xenobiotic metabolites with endogenous molecules). The reactions involve the coupling of xenobiotic acids and alcohols with endogenous intermediates of lipid synthesis (i. e., the acids with glycerol and cholesterol and the alcohols with the fatty acids). 

Even if their absorption is high, the bioavailability of many compounds may be limited by an extensive metabolism that can affect the in vivo activity profile irrespective of its route of administration. Metabolism is vital since it transforms absorbed nutrients into endogenous substances required to maintain body functions for xenobiotics, including phytochemicals, metabolism represents the key body defence mechanism that converts them into less harmful, water-soluble, and thus excretable, compounds. Lipophilic, low molecular weight xenobiotics that are readily absorbed and distributed are difficult to eliminate and thus may accumulate to hazardous levels. Therefore, most lipophilic xenobiotics are metabolized into hydrophilic conjugates that are less likely to pass through membranes and, hence, can be more easily eliminated via the kidney. 

Balaz M, Collins HA, Dahlstedt E, Anderson HL (2009) Synthesis of hydrophilic conjugated porphyrin dimers Pot one-photon and two-photon photodynamic therapy at NIR wavelengths. Org Biomol Chem 7 874—888... 

Methyl group (Section 2 7) The group —CH3 Mevalonic acid (Section 26 10) An intermediate in the biosyn thesis of steroids from acetyl coenzyme A Micelle (Section 19 5) A sphencal aggregate of species such as carboxylate salts of fatty acids that contain a lipophilic end and a hydrophilic end Micelles containing 50-100 car boxylate salts of fatty acids are soaps Michael addition (Sections 18 13 and 21 9) The conjugate ad dition of a carbanion (usually an enolate) to an a 3 unsatu rated carbonyl compound... 

Of particular interest when considering ionizable compounds is the difference of lipophilicity between the neutral species and one of its ionic forms, because ionization dramatically alters intramolecular interactions (such as electronic conjugation, internal ionic and hydrogen bonds, polarity, hydrophilic folding, and shielding). In a given solvent system, diff (log is approximately constant for compounds with similar chemical... 

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