Proteins, biochemical pathways

In this chapter, we review the interactions at the level of protein function, between opioid receptors and chemokine receptors, using both in vitro and in vivo model systems. As a part of this discussion, we also describe our current understanding of the biochemical pathway(s) that are involved in the heterologous desensitization process between these groups of receptors. 

The neurotransmitters of the ANS and the circulating catecholamines bind to specific receptors on the cell membranes of effector tissue. Each receptor is coupled to a G protein also embedded within the plasma membrane. Receptor stimulation causes activation of the G protein and formation of an intracellular chemical, the second messenger. (The neurotransmitter molecule, which cannot enter the cell, is the first messenger.) The function of intracellular second messenger molecules is to elicit tissue-specific biochemical events within the cell that alter the cell s activity. In this way, a given neurotransmitter may stimulate the same type of receptor on two different types of tissue and cause two different responses due to the presence of different biochemical pathways within each tissue. 

The neutrophil constitutes the first line of defence in protecting the host from invading bacterial and fungal pathogens. It is a highly potent cytotoxic cell and possesses an armoury of antimicrobial proteins and biochemical pathways that can be used in this protective role. 

It is important to appreciate that this principle of coupling-in-series underlies all biochemical pathways or processes, e.g. glycolysis, generation of ATP in the mitochondrion, protein synthesis from amino acids or a signal transduction pathway. Indeed, despite the fundamental importance of signalling pathways in biochemistry, a thermodynamic analysis of such a pathway has never been done, but the principles outlined above must apply even to signalling pathways. 

Of the four major classes of biochemicals (carbohydrates, proteins, nucleic acids and lipids), experiments have shown that the first three classes could have arisen through prebiotic chemistry. Although the biosynthesis of many natural products can be traced back to acetate (e.g. fatty acids, terpenes and polyketide biosynthesis) or amino acids (e.g. alkaloid biosynthesis), there are many whose biosynthetic origins are either obscure or result from a complex combination of pathways (Fig. 2). 

The tightly regulated pathway specifying aromatic amino acid biosynthesis within the plastid compartment implies maintenance of an amino acid pool to mediate regulation. Thus, we have concluded that loss to the cytoplasm of aromatic amino acids synthesized in the chloroplast compartment is unlikely (13). Yet a source of aromatic amino acids is needed in the cytosol to support protein synthesis. Furthermore, since the enzyme systems of the general phenylpropanoid pathway and its specialized branches of secondary metabolism are located in the cytosol (17), aromatic amino acids (especially L-phenylalanine) are also required in the cytosol as initial substrates for secondary metabolism. The simplest possibility would be that a second, complete pathway of aromatic amino acid biosynthesis exists in the cytosol. Ample precedent has been established for duplicate, major biochemical pathways (glycolysis and oxidative pentose phosphate cycle) of higher plants that are separated from one another in the plastid and cytosolic compartments (18). Evidence to support the hypothesis for a cytosolic pathway (1,13) and the various approaches underway to prove or disprove the dual-pathway hypothesis are summarized in this paper. 

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