Lipid-soluble ligands

Ahsanullah, M. and Florence, T. M. (1984). Toxicity of copper to the marine amphiphod Allorchestes compressa in the presence of water- and lipid-soluble ligands, Marine Biol., 84, 41-45. 

Interstitial retinol-binding protein may also carry other lipid-soluble ligands vitamin E is one possibility (Seetion II,F,2). This compound is present in bovine... 

A great number of ligands, such as the anions of ethylenediamine-NNN N -tetra-acetic acid (EDTA), described in detail by Schwarzen-bach and his school (29, 30), show a pronounced selectivity for alkaline earth and other metal cations (30). Because of the limited lipid solubility of these ligands and their complexes, such compounds are, however, not suited as ion carriers in lipophilic membranes (Fig. 2). The ability... 

Several biologic ligands are sufficiently lipid-soluble to cross the plasma membrane and act on intracellular receptors. One class of such ligands includes steroids (corticosteroids, mineralocorticoids, sex steroids, vitamin D), and thyroid hormone,... 

Since the discovery in 1964 that the antibiotic valinomydn exhibited alkali cation specificity in rat liver mitochondria, a new area of research has developed, based not only on biological systems but also on model systems such as crown ethers.484 The ability of neutral compounds to form lipid-soluble alkali and alkaline earth complexes was observed in 1951. The structure of the corresponding ligand, the anion of the antibiotic nigericin (78), was characterized as its silver salt in 1968.488 486 Silver was used as a heavy atom crystaUographically, since the Ag+ cation had a radius between that of Na+ and K+, which were the two alkali cations with which nigericin was most active. 

It seems likely that the future will see major developments in the use of metal complexes as bacteriocidal, viricidal, immunosuppressive, anti-arthritic and biocidal agents. One class of complexing agents that appears to have particular promise are the macrocyclic antibiotics, macrocyclic polyethers, polyamines and cryptates . In this group the ligand wraps around a metal ion to form a lipid-soluble complex... 

The chemical messenger is unable to cross the plasma membrane because of low lipid solubility. The messenger binds to specific plasma membrane receptors (integral membrane proteins). In the ligand-bound state the receptors activate either (1) an intrinsic ion channel (ionotropic receptors) or (2) a defined sequence of enzymes (metabotropic receptors). Table 6.5 shows examples of plasma membrane receptors. 

The membrane permeabilities of the free and complexed ligands also have important implications for their toxicity the lipid solubilities of the iron-free ligand affect the permeability of the blood-brain barrier and may cause CNS toxicity, while the relative solubilities of the free and complexed chelators affect body iron redistribution. 

Enhancing the lipid solubility of a ligand or of a metal complex to penetrate cell membranes which may appear desirable from the point of view of enhancing the rate of removal of the metal from the body may, vicariously, increase the toxicity of that ligand or its metal complex. For example, lipid soluble derivatives of EDTA are usually more toxic than the parent acid. 

FIGURE 11-40 Examples of hormones that bind to nuclear receptors. These and related lipid-soluble hormones bind to receptors located in the cytosol or nucleus. The ligand-receptor complex functions as a transcription activator. 

ZiMMERMANN S, MeNZEL CM, StUBEN D, TaRA-SCHEWSKI H and Sures B (2003b) Ligand dependent lipid solubility of the platinum group metals Pt, Pd and Rh as a measure of bioaccumulation. Environ Pollut 124 1-5... 

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