Purine Nucleotide Synthesis Disorders; Purine Salvage Disorders;

The biological importance of ribose relates to the fact that it is the rate-limiting compound that regulates the activity of the purine nucleotide pathway of adenine nucleotide metabolism. As such, ribose plays a central role in the synthesis of ATP, coenzyme-A, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), DNA, RNA, and other important cellular constituents. Ribose is the only known compound the body can use for performing this critical metabolic function.

Disorders of purines and pyrimidines - ScienceDirect

Ribose derivatives play a significant role in the body. Important ribose derivatives encompass those having phosphate groups attached at the 5 position, including mono-, di-, and triphosphate forms, and 3-5 cyclic monophosphates. Diphosphate dimers, known as coenzymes, form an essential class of compounds with ribose. When such purine and pyrimidine derivatives are coupled with ribose, they are known as nucleosides (bases attached to ribose). Phosphorylated nucleosides are known as nucleotides. When adenine (a purine derivative) is coupled to ribose it is known as adenosine. ATP is the 5’-triphosphate derivative of adenosine. (The adenine portion of ATP consists of ribose and adenine. The triphosphate portion of ATP consists of three phosphate molecules.)

Chapter 55 - Disorders of purines and pyrimidines

Disorders of purine and pyrimidine metabolism can result in an array of clinical ..

The mechanisms by which abnormalities in PRPP synthase cause neurological dysfunction are not known. PRPP serves as a cosubstrate for a diverse family of enzymes, only three of which are involved directly in purine metabolism. These include the first and rate-limiting step of de novo purine synthesis (amidophosphoribosyltransferase (AMPRT)) as well two recycling enzymes (APRT and HPRT). The clinical syndromes associated with PRPP synthase defects do not resemble the syndromes associated with APRT or HPRT defects. Thus neurological manifestations linked with PRPP synthase may result from alterations in nonpurine pathways.

Choline supplement benefit and side effects, bitartrate

Dr. Frank acknowledged the body’s capacity for synthesizing nucleic acids “de novo,” but rejected the presupposition that dietary (or exogenous) nucleic acids are not essential because the body can or will fulfill all of its own requirements. If this were the case, according to Frank, then one would not expect the often remarkable effects of dietary nucleic acid supplementation, both for aged or debilitated individuals, and for athletes or generally healthy persons. In both types of individuals, he describes nucleic acid supplementation as “unequivocal” in its effects (117).

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Dr. Frank explained the biochemical relation of vitamins and nucleic acids, and specifically used the example of the B-complex vitamins. In metabolizing Vitamin B3 (niacin or niacinamide), for example, the body requires energy for conversions that properly break down the vitamin into its usable components. Thus, cells convert niacin to coenzyme nicotinamide adenine dinucleotide (NAD), which may then be converted to NADP via a phosphate transfer from ATP. The initial reaction involves nicotinic acid with 5-phosphoribosyl 1-pyrophosphate to produce nicotinic mononucleotide (NMN).

He notes that phosphoribosyl pyrophosphate also is the basic compound for purine synthesis (and is formed from ribose-5-phosphate plus ATP). This indicates that the energy of level of a cell plays an essential role in the synthesis of NMN (the precursor of NAD), and therefore that the greater the rate of ATP synthesis, the greater the rate of synthesis of NMN. The next step in the metabolism of niacin involves NMN reacting with ATP to create desamido-NAD, where ATP acts both as a source of energy and a component of the NAD coenzyme.

Ultimately ATP is crucial to the formation of the NAD coenzyme (an important coenzyme in cellular energy metabolism). Thus, Dr. Frank states that higher Krebs cycle activity and oxygen-energy metabolism favors synthesis of NAD, given the availability of niacin (or niacinamide). Moreover, a higher level of niacin (or niacinamide) likewise would favor its own conversion into the active NAD coenzyme. Dr. Frank points to the evident relation of energy metabolism and NAD synthesis, wherein increased nucleic acid and nucleotide intake produces increased energy metabolism and ATP production, which in turn enables both more effective metabolism of niacin and further increases in cellular NAD. He therefore finds a very evident relationship between dietary nucleic acids and NAD with respect to energy production and related metabolism (151).

Dr. Frank relates similar processes for other vitamins (e.g., riboflavin and pantothenic acid) that he finds representative of the B-complex. From his own clinical experience, he relates his observation of definite increases in energy among subjects receiving high-dosage B-complex vitamins (e.g., 50–200 mg of thiamin daily plus other balanced B factors) given with high nucleic acid intake. His clinical observations correspond with his technical analysis of the synergistic biochemical relations between dietary nucleic acids and B vitamins in energy production.

Dr. Frank also discusses other vitamins in his books (e.g., Vitamin A). He concludes: “It is apparent that nucleic acid and nucleotide intake are most importantly related to vitamin usage and function and that the greater the nucleic acid intake, within limits not yet determined, the greater the synthesis and usage of many and perhaps most coenzymes” (153).

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Hereditary Motor Sensory Neuropathies: Charcot …

Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, MIT, Cambridge, MA
The synthesis of brain phosphatidyl choline may utilize three circulating precursors: choline; a pyrimidine (e.g., uridine, converted via UTP to brain CTP); and a PUFA (e.g., docosahexaenoic acid); phosphatidylethanolamine may utilize two of these, a pyrimidine and a PUFA.