5. ONIUM COMPOUNDS
233
Only future work will tell whether these differences are related to
kinetic characteristics of the enzymes involved or to energetic factors
involving the onium bond. It may be pointed out, however, that reversibility is easiest where an identical onium bond is formed (as in the
nicotinamide exchange) and absent where the exchange reaction would
require formation of an onium bond of a different type such as in the
exchange postulated in Reaction 25 which would interconvert a sulfonium and a pyridinium bond.
C. ENZYMATIC MECHANISMS IN THE FORMATION OF THE ONIUM BOND
Although onium compounds may be formed by the base exchange
reaction discussed in the preceding section, it is evident that this mechanism cannot account for the biogenesis of the onium bond since it
does not involve an actual increase in the number of onium compounds.
It has become clear in recent years that phosphate bond energy may be
utilized for the biosynthesis of the onium bond. Several examples for
such a mechanism have come to light: (a) the formation of nicotinamide riboside from ribose-1-phosphate and nicotinamide and of nicotinic acid ribotide from nicotinic acid and 5-phosphoribose-l-pyrophosphate; (b) the formation of S-adenosylmethionine from methionine and
ATP; and (c) the formation of thiamine from a phosphorylated pyrimidinehydroxymethyl moiety and thiazole.
1. Biosynthesis of Pyridinium Compounds
The formation of nicotinamide riboside is described in Eq. 26.
Θ
H + Nicotinamide + Ribose-1-phosphate «=± Nicotinamide riboside + Orthophosphate
(26)
As noted above (175) the equilibrium constant of the reaction favors
the back reaction, namely phosphorolysis of nicotinamide riboside.
Perhaps, if this is a significant pathway for the biogenesis of nicotinamide riboside, the reaction may be pulled in the forward direction
by coupling with any one of a number of reactions which utilize orthophosphate (e.g., oxidative phosphorylation, glycolysis, etc.). The cleavage of nicotinamide riboside has been discussed in the section on
energetics of the onium bond, and in more detail by Kalckar (166).
More recently evidence has accumulated to indicate that the synthesis
of DPN proceeds from nicotinic acid by the following consecutive
reactions (202).
Nicotinic acid + 5-Phosphoribose-l-pyrophosphate —>
Desamidonicotinamide mononucleotide + Pyrophosphate (27)
ATP + Desamidonicotinamide mononucleotide τ^. Desamido-DPN + Pyrophosphate
(28)
Desamido-DPN + Glutamine + ATP -> DPN + Glutamate + AMP + Pyrophosphate
(29)
233
Only future work will tell whether these differences are related to
kinetic characteristics of the enzymes involved or to energetic factors
involving the onium bond. It may be pointed out, however, that reversibility is easiest where an identical onium bond is formed (as in the
nicotinamide exchange) and absent where the exchange reaction would
require formation of an onium bond of a different type such as in the
exchange postulated in Reaction 25 which would interconvert a sulfonium and a pyridinium bond.
C. ENZYMATIC MECHANISMS IN THE FORMATION OF THE ONIUM BOND
Although onium compounds may be formed by the base exchange
reaction discussed in the preceding section, it is evident that this mechanism cannot account for the biogenesis of the onium bond since it
does not involve an actual increase in the number of onium compounds.
It has become clear in recent years that phosphate bond energy may be
utilized for the biosynthesis of the onium bond. Several examples for
such a mechanism have come to light: (a) the formation of nicotinamide riboside from ribose-1-phosphate and nicotinamide and of nicotinic acid ribotide from nicotinic acid and 5-phosphoribose-l-pyrophosphate; (b) the formation of S-adenosylmethionine from methionine and
ATP; and (c) the formation of thiamine from a phosphorylated pyrimidinehydroxymethyl moiety and thiazole.
1. Biosynthesis of Pyridinium Compounds
The formation of nicotinamide riboside is described in Eq. 26.
Θ
H + Nicotinamide + Ribose-1-phosphate «=± Nicotinamide riboside + Orthophosphate
(26)
As noted above (175) the equilibrium constant of the reaction favors
the back reaction, namely phosphorolysis of nicotinamide riboside.
Perhaps, if this is a significant pathway for the biogenesis of nicotinamide riboside, the reaction may be pulled in the forward direction
by coupling with any one of a number of reactions which utilize orthophosphate (e.g., oxidative phosphorylation, glycolysis, etc.). The cleavage of nicotinamide riboside has been discussed in the section on
energetics of the onium bond, and in more detail by Kalckar (166).
More recently evidence has accumulated to indicate that the synthesis
of DPN proceeds from nicotinic acid by the following consecutive
reactions (202).
Nicotinic acid + 5-Phosphoribose-l-pyrophosphate —>
Desamidonicotinamide mononucleotide + Pyrophosphate (27)
ATP + Desamidonicotinamide mononucleotide τ^. Desamido-DPN + Pyrophosphate
(28)
Desamido-DPN + Glutamine + ATP -> DPN + Glutamate + AMP + Pyrophosphate
(29)