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Ribose has multiple biochemical roles as a structural component of all ribonucleotides (i.e. ATP, GTP, NAD, NADP, and RNA) and is a structural precursor to 2-deoxyribose, an essential component of DNA. Although Ribose can enter the glycolytic pathway via the hexose monophosphate shunt (yielding glucose-6-phosphate from Ribose) and thus be metabolized like sugars such as glucose (or dextrose), sucrose (table sugar) and fructose ultimately entering the Krebs cycle, and the electron transport chain of oxidative phosphorylation, it’s value therapeutically is to bypass de novo synthesis of Ribose from glucose-6-phosphate (via the hexose monophosphate shunt) to support a more rapid replenishment of adenylate nucleotides in the cell. This is especially true in cardiac tissue, where glucose-6-phosphate dehydrogenase (the first enzyme in the hexose monophosphate shunt) is limited, thus making de novo synthesis of D-Ribose the rate limiting step in generating adenine nucleotides either through de novo synthesis or the salvage pathway where hypoxanthine is processed back into adenylate nucleotides.
When glucose is consumed, insulin is released into the blood stimulating glucose uptake into cells through an active transport mechanism. This process results in glucose being metabolized immediately as a fuel source or being stored in the form of glycogen (animal starch) or fat to be metabolized later. Interestingly, bolus Ribose administration also results in a spike in blood insulin levels followed a transient drop in blood glucose. This transient hypoglycemia has been well characterized in clinical pharmacokinetic studies sponsored by RiboCor.
Stressed Tissue Needs Ribose to Restore Normal Function
Every cell in the human body needs a continual supply of energy to maintain the array of metabolic activities essential to cellular function. This supply of energy is primarily provided through the synthesis of Adenosine Triphosphate (ATP) from Adenosine Diphosphate (ADP) and/or Adenosine Monophosphate (AMP) and is, normally, met without complication. However, in certain disease states, cellular ATP levels can become depleted due to hypoxic stress or other conditions leading to further loss of ATP as well as ADP and AMP resulting in a diminished adenylate pool. Depletion of the adenylate pool leads to compromised cellular function as occurs in heart failure heart or ischemic heart disease. This has been demonstrated in preclinical models as well as in the clinical setting. Furthermore, in fibromyalgia patients, skeletal tender points have been shown to have depleted ATP levels. Although the mechanistic basis for this is not known, decreased adenine nucleotide levels could lead to the symptomatic fatigue exhibited by the great majority of fibromyalgia patients.
Helping the body replenish the adenylate pool in target tissues may provide an effective treatment for patients with cardiovascular disease or fibromyalgia. Although, the body can produce Ribose via the hexose monophosphate shunt, it requires additional metabolic steps to accomplish this and, in some tissues such as cardiac muscle, synthesis of Ribose is the rate limiting step in the generation of ATP by either de novo synthesis or the salvage pathway. Administering supplemental Ribose can bypass the hexose monophosphate shunt providing a more rapid means of replenishing the adenylate pool. This could provide a significant therapeutic benefit to patients in a state of acute or chronic ATP depletion as observed in heart failure, ischemic heart disease and fibromyalgia.