Serine
Serine is a nonessential amino acid, which means that it is manufactured from other amino acids in the liver, and does not have to be obtained from the diet. It can also be made in the tissue from glycine or threonine. Its production, however, requires adequate amounts of vitamins B3 (niacin), B6 (pyridoxine), and B9 (folic acid) [Please refer to vitamin B-complex]. Serine is also the precursor of cysteine, methionine and glycine. It works in conjunction with alanine and glycine to help stabilize blood sugar. Serine helps form phospholipids, which is an important constituent of every cell in the body. It helps form the protective myelin sheath that covers the nerves, and is also important for the brain and central nervous system. It is also needed to produce tryptophan, the precursor of serotonin, a neurotransmitter which regulates mood, appetite, sleep, memory and learning. Both serotonin and tryptophan shortages have been linked to depression, insomnia, confusion, and anxiety. Good sources are soy and soy products, eggs, nuts and seeds, lentils, and peanuts.
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l-Serine is required for cellular and tissue growth and is particularly important in the immature brain where it acts as a crucial neurotrophic factor. In this study, the levels of amino acids and enzymes in the l-serine biosynthetic pathway were examined in the forebrain, cerebellum, liver, and kidney………. findings demonstrate that the expression of l-serine synthetic and degradative enzymes display reciprocal changes in the liver and kidney to increase l-serine and decrease d-serine levels under conditions of protein restriction, and that the brain is insulated from such changes.
o Antflick, JE, Baker, GB, & Hampson, DR. (2009). The Effects of a low protein diet on amino acids and enzymes in the serine synthesis pathway in mice . Amino Acids.Serine deficiency disorders are rare defects in the biosynthesis of the amino acid L-serine. At present two disorders have been reported: 3-phosphoglycerate dehydrogenase deficiency and 3-phosphoserine phosphatase deficiency. These enzyme defects lead to severe neurological symptoms such as congenital microcephaly and severe psychomotor retardation and in addition in patients with 3-phosphoglycerate dehydrogenase deficiency to intractable seizures. These symptoms respond to a variable degree to treatment with L-serine, sometimes combined with glycine.
o de Koning, TJ. (2006). Treatment with amino acids in serine deficiency disorders. Journal of Inherited Metabolic Disease , 29(2-3), 347-51.
Previous research has revealed that major depression is accompanied by disorders in excitatory amino acids, e.g. glutamate and aspartate, and alterations in serum levels of other amino acids, e.g. serine, glycine and taurine. The aim of the present study was to examine serum levels of aspartate, asparagine, glutamate, glutamine, serine, glycine, threonine, histidine, alanine, taurine and arginine in major depression patients with treatment-resistant depression (TRD)……………. The results suggest that alterations in serum levels of aspartate, asparagine, serine, threonine and taurine may predict the subsequent response to treatment with antidepressants.
o Maes, M, Verkerk, R, Vandoolaeghe, E, Lin, A, & Scharpé, S. (2007). Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity. Acta Psychiatrica Scandinavica, 97(4), 302-8.
The N-methyl-D-aspartate (NMDA) receptors play key roles in excitatory neurotransmission and are involved in several important processes, including learning, behavior, and synaptic plasticity………….In addition to glutamate, the NMDA receptor activity was believed to be regulated by the coagonist glycine. More recently, D-serine has also been proposed to play a role as a key coagonist for NMDA receptor activity and neurotoxicity………. D-Serine was originally shown to be exclusively made in astrocytes, indicating a possible role as a gliotransmitter. Nevertheless, recent data indicate that D-serine has a neuronal origin as well.
o Wolosker, H. (2007). Nmda receptor regulation by d-serine: new findings and perspectives.. Mol Neurobiol, 36(2), 152-64.D-Serine has recently been identified as a major gliotransmitter in the mammal central nervous system (CNS). The distribution of D-serine is analogous to the N-methyl-D-aspartate (NMDA)-type glutamate receptors in the brain. D-Serine is as potent as glycine as a coagonist at the glycine-binding site of NMDA receptors. Thus, D-serine has been considered as an endogenous ligand of the NMDA receptors in the brain………. The present review highlights the most recent findings on the molecular mechanisms of controlling D-serine metabolism in the CNS, the physiological role of D-serine in synaptic plasticity, and the pathological relevance of D-serine to schizophrenia, excitotoxicity- and neuroinflammation-induced neuronal death as well as neuropathic pain.
o Ying-Luan, Z, Zhao, YL, & Mori, H. (2007). Role of d-serine in the mammalian brain. Brain Nerve, 59(7), 725-30.This study was carried out to investigate plasma levels of excitatory amino acids, such as glutamate and aspartate, and glutamine, serine, glycine, taurine and histidine in major depression. The plasma amino acids were determined by means of HPLC in 22 normal controls and 25 unmedicated patients with major depression…………. The results suggest that major depression is accompanied by perturbations in the serine/glycine ratio, excitatory amino acids, such as glutamate, and inhibitory amino acids, such as taurine.
o Altamura, C, Maes, M, Dai, J, & Meltzer, HY. (1995). Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression. European Neuropsychopharmacology, 5(12), 71-5.Until the last decade, it was widely accepted that D-amino acids had no functional role in higher organisms, but that they were restricted to lower organisms, such as bacteria, where they are integrated into the proteoglycans of the cell wall. However, D-serine proved to be an effective coagonist at the "glycine-binding" site of the N-methyl-D-aspartate (NMDA) glutamate receptors, and this observation led to chemical analyses that have now revealed the presence of high levels of D-serine in the central nervous system, including many regions of the brain and retina…………… D-serine must be added to the list of agents through which glial cells participate in controlling the excitability of neurons.
o Miller, RF. (2004). D-serine as a glial modulator of nerve cells. Glia, 47(3), 275-83.
Abundant recent evidence favors a neurotransmitter/neuromodulator role for D-serine. D-serine is synthesized from L-serine by serine racemase in astrocytic glia that ensheath synapses, especially in regions of the brain that are enriched in NMDA-glutamate receptors. D-serine is more potent than glycine at activating the ‘glycine’ site of these receptors………. Thus, glutamate triggers the release of D-serine so that the two amino acids can act together on postsynaptic NMDA receptors. D-serine also plays a role in neural development, being released from Bergmann glia to chemokinetically enhance the migration of granule cell cerebellar neurons from the external to the internal granular layer.
o Mustafa, AK, Kim, PM, & Snyder, SH. (2004). D-serine as a putative glial neurotransmitter. Neuron Glia Biol, 1(3), 275-81.
The mammalian brain contains unusually high levels of D-serine, a D-amino acid previously thought to be restricted to some bacteria and insects. In the last few years, studies from several groups have demonstrated that D-serine is a physiological co-agonist of the N-methyl D-aspartate (NMDA) type of glutamate receptor -- a key excitatory neurotransmitter receptor in the brain. D-Serine binds with high affinity to a co-agonist site at the NMDA receptors and, along with glutamate, mediates several important physiological and pathological processes, including NMDA receptor transmission, synaptic plasticity and neurotoxicity. In recent years, biosynthetic, degradative and release pathways for D-serine have been identified, indicating that D-serine may function as a transmitter. At first, D-serine was described in astrocytes, a class of glial cells that ensheathes neurons and release several transmitters that modulate neurotransmission. This led to the notion that D-serine is a glia-derived transmitter (or gliotransmitter). However, recent data indicate that serine racemase, the D-serine biosynthetic enzyme, is widely expressed in neurons of the brain, suggesting that D-serine also has a neuronal origin.
o Wolosker, H, Dumin, E, Balan, L, & Foltyn, VN. (2008). D-amino acids in the brain: d-serine in neurotransmission and neurodegeneration. FEBS J, 275(14), 3514-26.
D-Serine, an endogenous modulator of NMDA receptors has been shown to play a vital role in many neuropsychiatric functions such as learning, memory, nociception and implicated in pathological conditions like schizophrenia and Alzheimer's disease.
o Sethuraman, RF, Lee, TL, & Tachibana, S. (2009). D-serine regulation: a possible therapeutic approach for central nervous diseases and chronic pain. Mini Rev Med Chem, 94(7), 813-9.