Uridine and PC

Whether the human body contains ten trillion or a hundred trillion cells makes little difference. It would take several lifetimes to count them. What does matter is how those cells communicate with each other, how they share messages about function, repair and reproduction. The basic unit of structure and function of living things, the cell is the building block of life. The word “cell” means “small room,” a fitting term for a structure that houses an assembly of bodies that direct life processes. Environment, genetics and lifestyle exert a greater influence on a cell’s viability than many people can imagine. To remain healthy, the cell must overcome insults every day. Air and water degradation, tobacco and alcohol use and abuse, and wretched eating habits are major participants in the unremitting assault on cellular equilibrium.

Of the several compounds vital to the cell’s structure and function, phosphatidylcholine, at 50% or more the major constituent of the cell membrane, is deemed paramount. As a circus would be useless without a tent, so would be the cell without its membrane. Phosphatidylcholine, abbreviated as PC, is a ubiquitous, naturally occurring phospholipid composed of a phosphate group, two fatty acids, and choline. Often confused with lecithin, PC verifiably stands alone, while lecithin is a mix of several second-team players that make a perfect emulsifier for mayonnaise but an inferior contributor to cellular integrity and health. PC is responsible for the surfactants critical to lung function and gastrointestinal stability, and is the precursor to the neurotransmitter, acetylcholine, responsible for arousal, learning, memory and motor activity.

PC is one of four phospholipids that comprise the membrane. The others are phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI). Without its membrane, the cell would cease to function altogether—the Krebs cycle would be interrupted and there would be no energy and thus no life. It has been postulated that almost one third of all the genetic output of the human DNA cache is rooted in the membrane (Mouritsen, 2005).

The fluid character of the membrane is provided by essential fatty acids (EFA), both the omega-6 and omega-3 that the body must get from dietary sources. It’s not enough that we supply the proper amount of EFA’s; the ratio is perhaps more important. The proportion of n-6 to n-3 fats has been established as 4:1, as discovered in studies that have examined improvement in quality of life for both the well and the infirm (Yehuda, 1993, 1996) (Simopoulos, 2002, 2004, 2008).

All biological processes—every single one— rely on PC for their unimpeded activity. Information flowing from DNA to RNA to proteins needs PC; the manufacture of cellular energy and intracellular communication or signal transduction demands it. EFA-rich PC fluidizes the cell membrane to allow the smooth passage of vital substances into the cytoplasm and the movement of detritus out. It is well-accepted that some diseases, such as certain cancers, liver disease, neurological disorders and cell death, are related to a decrease in cell membrane fluidization resulting from a deficit of PC (PDR, 2001).

The shape of the PC molecule is ideal to serve as the basic structural unit of the biological membrane. The kink in the polyunsaturated fatty acid (PUFA) chain affords fluidity that acts to balance the lipids—and cholesterol—that are not members of the bilayer family. Lined up, shoulder-to-shoulder, PC molecules organize themselves into a protective phalanx that guards every cell and every organelle within. PC’s two tails are hydrophobic, face the inside of the cell and directly oppose others of their kind, thus forming an inner and an outer leaf. The hydrophilic head group faces the watery environs of which the body is largely made. The channels, gates and receptors that occupy the membrane help to run the machinery of life. Having both hydrophobic and hydrophilic properties, PC is an amphiphilic molecule. Its arrangement in the cell membrane parallels the structure, activity and function of a liposome.

A liposome is a tiny bubble (a vesicle) made from the same material as the cell membrane. But a liposome can be filled with medications and be used to deliver drugs in the treatment of some diseases, such as cancers. The core of a liposome is almost always aqueous and the circumference always a hydrophobic bilayer.

Hydrophobic substances, including pharmacologically active non-drugs, may be encapsulated by a liposome to increase their water solubility, thereby improving bioavailability and absorption. Liposomal delivery protects the contents from degradation in blood, thus increasing efficacy and reducing the possibility of a toxic event. By manipulating the lipid bilayer, scientists can create a time-released product that targets delivery of the material. A liposome can be made when a legitimate phospholipid, such as phosphatidylcholine (not lecithin) is placed in water and agitated or sonicated to form a bilayer. Low shear rates will form multilamellar liposomes, which resemble the layers of an onion. Sonication is the application of ultra sound to disrupt the stable condition of matter, allowing the lipid perimeter to re-amalgamate around the chosen material. (It works especially well to deactivate bacteria and to clean things, like jewelry, by breaking intermolecular interactions.) Vitamins, antigens, and even monoclonal antibodies may constitute a liposomal core.

One bioactive candidate substance that has garnered attention recently is uridine, a nucleoside component of RNA made from one molecule of uracil and one molecule of D-ribose. Uracil is a pyrimidine that replaces the thymine in DNA to make RNA. Together, pyrimidines and purines make both DNA and RNA. Ribose, or rather D-ribose as found naturally, is a simple sugar (monosaccharide) that forms the backbone of RNA. It’s related to the deoxyribose found in DNA.

What’s the difference between DNA and RNA? That’s a good question. Both are nucleic acids, but they differ in that RNA is single-stranded while DNA is double-stranded. In RNA, uracil is an unmethylated form of thymine. It might be easier to view RNA as a carrier of messages and DNA as the owner’s manual for cell replication. There’s more, but that can be saved for another time.

Uridine is the active ingredient of its compounds, some of which may be phosphorylated or acetylated. It’s made by the liver from some foods, notably tomatoes, sugarcane, brewer’s yeast, broccoli and organ meats. Eating foods that are rich in RNA, however, may lead to health concerns because RNA also contains purines, the elements (adenosine and guanosine) responsible for conditions such as gout. But on the bright side—the very bright side—uridine as a supplement, combined with the essential n-3 fatty acids EPA and DHA, has been found to be as effective an antidepressant as commonly prescribed medications, such as Prozac® and other SSRI’s (Carlezon, 2005). Not only is uridine associated with positive mental health outcomes, but also with the resolution of mitochondrial disorders, some of which may be induced by certain medications, particularly those related to treatment of HIV and orotic aciduria, the latter a genetic disorder characterized by retarded growth, macrocytic anemia, and leukopenia, accompanied by urinary excretion of large amounts of orotic acid. (Weinberg, 2011).

In its monophosphate form, uridine is synthesized de novo from glycine, the smallest of the twenty amino acids found in proteins. Glycine is non-essential and can be manufactured by the body from another amino acid, serine. In the central nervous system, glycine acts as an inhibitory neurotransmitter, with primary activity in the brainstem, spinal cord, and retina. Alone, it’s been used to enhance sleep quality (Yamadera, 2007). Uridine monophosphate is successfully converted to its di- and triphosphate forms, eventuating to a factor crucial in the formation of dendritic spines, which are bodies that protrude from the dendrites of a neuron in order to receive messages across the synapse. They act as a storage unit, a kind of capacitor, to assist the transmission of electrical signals to the neuron’s cell body.

Dendritic spines are essential for intellectual ability, where their plasticity is associated with motivation, learning and memory. Long-term memory is mediated by the growth of new spines or the enlargement of existing ones. This helps to reinforce specific neural pathways. Because their lifespan is heavily influenced by (sensory) input activity, spine dynamics play a role in the maintenance of memory over a lifetime. In youngsters, the rate of spine turnover is relatively high, producing a net loss because the rate of elimination surpasses the rate of formation. Spines remain persistent in adulthood (Alvarez, 2007) (Zuo, 2005).

A form of uridine known as triacetyluridine is classified as a pro-drug because it serves as a precursor to an endogenous compound—cytidine triphosphate (CTP)—that has the capability to address the progressive degeneration of dopaminergic neurons that characterize Parkinson’s disease (Cansev, 2008). In its several forms, uridine promotes neurite outgrowth and stimulates downstream messengers that modulate neurotransmitter release (Krügel, 2001) (Shoji-Kasai, 2002) and helps to increase the number of dendritic spines in the brain (Sakamoto, 2007).

Living in an impoverished sensory environment retards memory development and impairs its function in adulthood. Brain phosphatidylcholine synthesis uses uridine as an element of its totality and, in combination with polyunsaturated fatty acids, has been found to improve cognitions in young and aged laboratory animals and humans, much the same as would be expected from living in an enriched sensory environment from birth (Holguin, Aug. 2008). In later study by Holguin, phosphatidylcholine constituents, PUFA omega-3’s, and uridine combined to make a cocktail shown to increase total brain phospholipids and to enhance cognitive function by increasing synaptic membrane content (Holguin, Nov., 2008).

When cerebral function is disrupted and presents with periodic convulsive seizures, a diagnosis of epilepsy may be anticipated. Here, a sudden discharge of excess electrical activity may affect many areas of the brain or focus on only a few, resulting in either grand mal or petite mal episodes, the former being characterized by loss of consciousness and the latter by clouded consciousness. More than one condition may elicit seizures, making etiology difficult to pinpoint, although genes, head trauma, dementia, or developmental disorders, among others, may be implicated. Anti-epileptic drugs, because of their limited efficacy and unwelcome side effects, have spurred an interest in new, perhaps even alternative, treatments. The Neuroscience Center at Dartmouth investigated uridine as a possible endogenous anti-epileptic modulator in specific patterns of epilepsy. It was learned that administration of uridine effected a reduction in EEG spike frequency and improved visual spatial memory in laboratory animals exposed to lithium-pilocarpine-induced status epilepticus, which may entail hippocampus damage (Müller, 2009) (Zhao, 2006).

Of greater concern to the general public is Alzheimer’s disease (AD), whether addressing prevention or the presence of inchoate dementia. Often beginning with slight memory loss and culminating with the inability to exercise judgment and to communicate effectively, Alzheimer’s has been the target of a number of pharmaceutical approaches. Decades-old research from the U. of California identified synapse degradation as a major factor in the onset of cognitive impairment (Terry, 1991). Years later, a medical food containing phosphatide precursors (PC) and associated cofactors, including uridine and PUFA’s, was found to improve memory in mild AD patients (Scheltens, 2010). Subjects suffering mild cognitive decline in the absence of dementia also found significant benefit from this medical food. In both mild AD and incipient cognitive impairment, total phospholipid and fatty acid levels were deficient (Conquer, 2000). Herein lies but one rationale for marrying uridine to PC. Because the typical American diet lacks the nutritive wholeness of the past, based on the shared rogueries of perfunctory agricultural practices and food handling, and on the dubious ways of too many home and commercial kitchens, supplementation of uridine and PC might be a prudent habit to cultivate.


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*These statements have not been evaluated by the FDA. These products are not intended to treat, diagnose, cure, or prevent any disease.

Rao Muralikrishna Adibhatla, James F. Hatcher, Eric C. Larsen, Xinzhi Chen, Dandan Sun and, Francis H. C. Tsao

CDP-choline Significantly Restores Phosphatidylcholine Levels by Differentially Affecting Phospholipase A2 and CTP: Phosphocholine Cytidylyltransferase after Stroke* The Journal of Biological Chemistry. March 10, 2006; 281 6718-6725.

Alvarez VA, Sabatini BL. Anatomical and physiological plasticity of dendritic spines. Annu Rev Neurosci. 2007;30:79-97.

Debabrata Banerjee, Richard Gorlick, Rebecca Sowers, Joseph S Miles, Wotcjek Rode, Nancy Kemeny, Joseph R Bertino Lack of uridine monophosphate kinase (UMPK) expression in tumor samples from colorectal cancer patients clinically resistant to 5-fluorouracil

Proc Am Soc Clin Oncol 21: 2002 (abstr 350) 2002 ASCO Annual Meeting. Poster Discussion Session, Pharmacology

D. Harshad Bhatt, Shengxiang Zhang, and Wen-Biao Gan Dendritic Spine Dynamics Annual Review of Physiology. Mar 2009; Vol. 71: 261-282

Cansev M, Watkins CJ, van der Beek EM, Wurtman RJ. Oral uridine-5’-monophosphate (UMP) increases brain CDP-choline levels in gerbils. Brain Res. 2005 Oct 5;1058(1-2):101-8. Epub 2005 Aug 29.

Cansev M, Wurtman RJ. Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils. Neuroscience. 2007 Aug 24;148(2):421-31.

Cansev M, Wurtman RJ, Sakamoto T, Ulus IH. Oral administration of circulating precursors for membrane phosphatides canpromote the synthesis of new brain synapses. Alzheimers Dement. 2008 Jan;4(1 Suppl 1):S153-68.

Cansev M, Ulus IH, Wang L, Maher TJ, Wurtman RJ. Restorative effects of uridine plus docosahexaenoic acid in a rat model of Parkinson’s disease. Neurosci Res. 2008 Nov;62(3):206-9.

Cansev M, Marzloff G, Sakamoto T, Ulus IH, Wurtman RJ. Giving uridine and/or docosahexaenoic acid orally to rat dams during gestation and nursing increases synaptic elements in brains of weanling pups. Dev Neurosci. 2009;31(3):181-92.

Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005 Feb 15;57(4):343-50.

Chang KC, Oh JY, In YS, Kim MK, Shin KC, Wee WR, Lee JH, Park MG. Preliminary effects of oral uridine on the ocular surface in dry eye patients. J Korean Med Sci. 2009 Aug;24(4):701-7.

Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids. 2000 Dec;35(12):1305-12.

De Bruin NM, Kiliaan AJ, De Wilde MC, Broersen LM. Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats. Neurobiol Learn Mem. 2003 Jul;80(1):63-79.

Dobolyi A, Juhász G, Kovács Z, Kardos J. Uridine function in the central nervous system. Curr Top Med Chem. 2011;11(8):1058-67.

Gella A, Ponce J, Cussó R, Durany N. Effect of the nucleotides CMP and UMP on exhaustion in exercise rats. J Physiol Biochem. 2008 Mar;64(1):9-17.

Gibellini F, Smith TK. The Kennedy pathway--De novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB Life. 2010 Jun;62(6):414-28.

J. Hartinger, P. Veselý, E. Matoušková, S. Argalacsová, L. Petruželka, and I. Netíková Local Treatment of Hand-Foot Syndrome with Uridine/Thymidine: In Vitro Appraisal on a Human Keratinocyte Cell Line HaCaT The Scientific World Journal. Volume 2012 (2012), Article ID 421325, 6 pages

Holguin S, Huang Y, Liu J, Wurtman R. Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats. Behav Brain Res. 2008 Aug 5;191(1):11-6.

Holguin S, Martinez J, Chow C, Wurtman R. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J. 2008 Nov;22(11):3938-46.

Holtmaat AJ, Trachtenberg JT, Wilbrecht L, Shepherd GM, Zhang X, Knott GW, Svoboda K. Transient and persistent dendritic spines in the neocortex in vivo. Neuron. 2005 Jan 20;45(2):279-91.

Jensen JE, Daniels M, Haws C, Bolo NR, Lyoo IK, Yoon SJ, Cohen BM, Stoll AL, Rusche JR, Renshaw PF. Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients. Exp Clin Psychopharmacol. 2008 Jun;16(3):199-206.

Jonas DA, Elmadfa I, Engel KH, Heller KJ, Kozianowski G, König A, Müller D, Narbonne JF, Wackernagel W, Kleiner J. Safety considerations of DNA in food. Ann Nutr Metab. 2001;45(6):235-54.

Douglas G. Kondo, M.D., Young-Hoon Sung, M.D., Tracy L. Hellem, B.S., Kristen K. Delmastro, B.S., Eun-Kee Jeong, Ph.D., Namkug Kim, Ph.D., Xianfeng Shi, Ph.D., and Perry F. Renshaw, M.D., Ph.D., M.B.A. Open-Label Uridine for Treatment of Depressed Adolescents with Bipolar Disorder J Child Adolesc Psychopharmacol. 2011 April; 21(2): 171–175.

Krügel U, Kittner H, Franke H, Illes P. Stimulation of P2 receptors in the ventral tegmental area enhances dopaminergic mechanisms in vivo. Neuropharmacology. 2001 Jun;40(8):1084-93.

Takayuki Matsumoto, Rita C. Tostes, and R. Clinton Webb  The Role of Uridine Adenosine Tetraphosphate in the Vascular System Advances in Pharmacological SciencesVolume 2011 (2011), Article ID 435132, 7 pages

Mouritsen, Ole G. “Life—As a Matter of Fat.” Berlin/Heidelberg: Springer-Verlag, 2005. P. 16

Kakali Mukherjee, M. Venkatesh, P. Venkatesh, B.P. Saha, Pulok K. Mukherjee Effect of soy phosphatidyl choline on the bioavailability and nutritional health benefits of resveratrol Food Research International. May 2011;44(4): 1088-1093

Müller CJ, Bankstahl M, Gröticke I, Löscher W. Pilocarpine vs. lithium-pilocarpine for induction of status epilepticus in mice: development of spontaneous seizures, behavioral alterations and neuronal damage. Eur J Pharmacol. 2009 Oct 1;619(1-3):15-24. Epub 2009 Jul 24.

Nimchinsky EA, Sabatini BL, Svoboda K. Structure and function of dendritic spines. Annu Rev Physiol. 2002;64:313-53.

Parry TE, Blackmore JA. Serum “uracil+uridine” levels before and after vitamin B12 therapy in pernicious anaemia. Br J Haematol. 1976 Dec;34(4):575-9.

PDR for Nutritional Supplements. Ed: Sheldon Hendler, PhD, MD, 2001. Montvale, NJ: Thompson, p 352

Pooler AM, Guez DH, Benedictus R, Wurtman RJ. Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12 . Neuroscience. 2005;134(1):207-14.

Sakamoto T, Cansev M, Wurtman RJ. Oral supplementation with docosahexaenoic acid and uridine-5’-monophosphate increases dendritic spine density in adult gerbil hippocampus. Brain Res. 2007 Nov 28;1182:50-9. Epub 2007 Sep 21.

Scheltens P, Kamphuis PJ, Verhey FR, Olde Rikkert MG, Wurtman RJ, Wilkinson D, Twisk JW, Kurz A. Efficacy of a medical food in mild Alzheimer’s disease: A randomized, controlled trial. Alzheimers Dement. 2010 Jan;6(1):1-10.e1.

Secades JJ, Frontera G CDP-choline: pharmacological and clinical review. Methods Find Exp Clin Pharmacol. 1995 Oct;17 Suppl B:1-54.

Shoji-Kasai Y, Itakura M, Kataoka M, Yamamori S, Takahashi M. Protein kinase C-mediated translocation of secretory vesicles to plasma membrane and enhancement of neurotransmitter release from PC12 cells.Eur J Neurosci. 2002 Apr;15(8):1390-4.

Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002 Oct;56(8):365-79.

Simopoulos, A. P. Omega-6/omega-3 essential fatty acid ratio and chronic diseases. Food Reviews International, 2004 (Vol. 20) (No. 1) 77-90

Artemis P. Simopoulos The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases Experimental Biology and Medicine  233:674-688 (2008)

Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991 Oct;30(4):572-80.

Ulus IH, Watkins CJ, Cansev M, Wurtman RJ. Cytidine and uridine increase striatal CDP-choline levels without decreasing acetylcholine synthesis or release. Cell Mol Neurobiol. 2006 Jul-Aug;26(4-6):563-77. Epub 2006 Apr 25.

Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary uridine-5’-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27(1):137-45.

Melissa E. Weinberg, Mark C. Roman, Peyton Jacob, Michael Wen, Polly Cheung, Ulrich A. Walker, Kathleen Mulligan, and Morris Schambelan Enhanced Uridine Bioavailability Following Administration of a Triacetyluridine-Rich Nutritional Supplement PLoS One. 2011; 6(2): e14709.

Wurtman RJ, Ulus IH, Cansev M, Watkins CJ, Wang L, Marzloff G. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006 May 9;1088(1):83-92.

Wurtman RJ, Cansev M, Ulus IH. Synapse Formation Is Enhanced by Oral Administration of Uridine and DHA, the Circulating Precursors of Brain Phosphatides. J Nutr Health Aging. 2009 Mar;13(3):189-97.

Wataru Yamadera, Kentaro Inagawa, Shintaro Chiba, Makoto Bannai, Michio Takahashi, Kazuhiko Nakayama Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes Sleep and Biological Rhythms. Volume 5, Issue 2, pages 126–131, April 2007

Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Ka T, Fukuchi M, Hada T. Effect of beer on the plasma concentrations of uridine and purine bases. Metabolism. 2002 Oct;51(10):1317-23.

Yehuda S, Carasso RL.

Modulation of learning, pain thresholds, and thermoregulation in the rat by preparations of free purified alpha-linolenic and linoleic acids: determination of the optimal omega 3-to-omega 6 ratio. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10345-9.

Yehuda S, Rabinovtz S, Carasso RL, Mostofsky DI. Essential fatty acids preparation (SR-3) improves Alzheimer’s patients quality of life.

Int J Neurosci. 1996 Nov;87(3-4):141-9. Ying H, Chen X, Cao H, Xiong J, Hong Y, Bai J, Li Z. Enhanced uridine diphosphate N-acetylglucosamine


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