General Outline of the Pathway

Early experiments by Bernheim, Felix, Sealock, and their co-workers on oxidation of tyrosine by liver breis showed an uptake of four atoms of oxygen per mole of tyrosine, with the production of one molecule each of carbon dioxide and acetoacetate, but no ammonia (60, 61, 261, 262, 789, 976). Felix and Zorn (261) found alanine to be formed and considered this to arise from a direct splitting of the tyrosine side chain. Although the experiments with man and intact animals already described made it seem very probable that p-hydroxyphenylpyruvic acid and homogentisic acid were normal intermediates in tyrosine metabolism, and although homogentisic acid was known to be readily metabolized by normal liver (e.g., 208, 695, 976) Felix and co-workers (262) considered p-hydroxyphenylpy-ruvic acid and homogentisic acid not to be intermediates in the breakdown of tyrosine by the liver system. 

Isotopic experiments shed more light on the contradictory evidence. Weinhouse and Millington (905) incubated liver slices with tyrosine labeled with in the 8-position of the side chain, and found that the activity appeared in the methylene carbon of acetoacetate. Schepartz and Gurin (772, 773) incubated with liver slices phenylalanine labeled with in the carboxyl group or a-position, or in positions 1, 3, and 5 of the aromatic ring. They found that the a-carbon of the side chain became the carboxyl-carbon of acetoacetate either C-1 or C-3 of the ring became the terminal methyl 

Diagram 8. Summary of the steps involved in the degradation of phenylalanine and tyrosine to fumaric and acetoacetic acids by the principal pathway used by animals and man. 

This scheme has been confirmed in numerous experiments, especially those of Felix and co-workers (257) in which they re-examined and clarified their earlier results. 

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Biosynthesis and Metabolism.—A general outline of the pathways and mechanisms of carotenoid biosynthesis has been presented,""" and carotenoid biosynthesis in plants has been reviewed."" ... 

The general outline of the pathways of amino acid biosynthesis is shown in Figure 2.1. It should be stressed that the detailed enzymology of these pathways is far better understood in bacteria and some eucaryotic microorganisms than in higher plants indeed, in most plant species, information on the relevant enzymology is fragmentary. As will be seen later. 

Recent development of the Heck reaction has also led to greater understanding of its mechanistic details. The general outlines of the mechanism of the Heck reaction have been appreciated since the 1970s and are discussed in numerous reviews [2,3]. More recently, two distinct pathways, termed the neutral and cationic pathways, have been recognized [2c-g,3,7,8,9]. The neutral pathway is followed for unsaturated halide substrates and is outlined in Scheme 8G. 1 for the Heck cyclization of an aryl halide. Thus, oxidative addition of the aryl halide 1.2 to a (bisphosphine)Pd(O) (1.1) catalyst generates intermediate 1.3. Coordination of... 

Figure 2.1 General outline of the biosynthetic pathway to the formation of main monoterpene skeletons.

Chapters 7 through 11 outline details of biochemical reactions involved in the biodegradation of the major groups of aliphatic, carbocyclic aromatic, and heterocyclic componnds. Although emphasis is placed on the pathways, rather general acconnts of the enzymes involved and the genetics are provided where they are available. 

An outline of the shikimate pathway from carbohydrate through chorismate to the aromatic amino acids and other metabolically important compounds is shown in Figure 1.1. The major branch point occurs at chorismate and that part of the metabolic sequence from carbohydrate to chorismate is generally referred to as the common pathway. 

While the mechanistic scheme as outlined so far accounts for the majority of structural changes in ring A-dienone isomerizations, a few cases require modifications of this general pathway. The B-nor dienone (215) is transformed exclusively to the linear dienone (217) in dioxane solution. The preferential fission of the 5,10-bond in the hypothetical precursor (216) has... 

At least two pathways have been proposed for the Nenitzescu reaction. The mechanism outlined below is generally accepted." Illustrated here is the indolization of the 1,4-benzoquinone (4) with ethyl 3-aminocrotonate (5). The mechanism consists of four stages (I) Michael addition of the carbon terminal of the enamine 5 to quinone 4 (II) Oxidation of the resulting hydroquinone 10 to the quinone 11 either by the starting quinone 4 or the quinonimmonium intermediate 13, which is generated at a later stage (HI) Cyclization of the quinone adduct 11, if in the cw-configuration, to the carbinolamine 12 or quinonimmonium intermediate 13 (IV) Reduction of the intermediates 12 or 13 to the 5-hydroxyindole 6 by the initial hydroquinone adduct 7 (or 8, 9,10). 

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