Picolinate Carboxylase and Nonenzymic Cyclization to Quinolinic Acid

1 Picolinate Carboxylase and Nonenzymic Cyclization to Quinolinic Acid 

The result of this is that at low rates of flux through the kynurenine pathway, which result in concentrations of aminocarhoxymuconic semialdehyde below that at which picolinate carboxylase is saturated, most of the flux will be byway of the enzyme-catalyzed pathway, leading to oxidation. There will be Utde accumulation of aminocarhoxymuconic semialdehyde to undergo nonenzymic cyclization. As the rate of formation of aminocarhoxymuconic semialdehyde increases, and picolinate carboxylase nears saturation, there will be an increasing amount available to undergo the nonenzymic reaction and onward metabolism to NAD. Thus, there is not a simple stoichiometric relationship between tryptophan and niacin, and the equivalence of the two coenzyme precursors will vary as the amount of tryptophan to be metabolized and the rate of metabolism vary. 

As might be expected, the synthesis of NAD from tryptophan is inversely related to the activity of picolinate carboxylase. Inhibition with pyrazinamide results in increased availability of aminocarhoxymuconic semialdehyde, and hence increased NAD formation. Equally, activation of picolinate carboxylase results in reduced availability of aminocarhoxymuconic semialdehyde for cyclization, and hence a reduced formation of NAD. 

which have some 30- to 50-fold higher activity of picolinate carboxylase than other species, are entirely reliant on a dietary source of preformed niacin, and are not capable of any significant synthesis of NAD from tryptophan. 

It is thus apparent that the utilization of tryptophan as a precursor for NAD synthesis depends on both the amount of tryptophan to be metabolized and also the rate of metabolic flux through the pathway. The activities of three 

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