Extraversion and introversion
The trait of extraversion–introversion is a central dimension of human personality theories. The terms introversion and extraversion were popularized by Carl Jung, although both the popular understanding and psychological usage differ from his original intent. Extraversion tends to be manifested in outgoing, energetic behavior, whereas introversion is manifested in more reserved and solitary behavior. All comprehensive models of personality include these concepts in various forms. Examples include the Big Five model, Jung's analytical psychology, Hans Eysenck's three-factor model, Raymond Cattell's 16 personality factors, the Minnesota Multiphasic Personality Inventory, the Myers–Briggs Type Indicator. Extraversion and introversion are viewed as a single continuum, so to be high in one necessitates being low in the other. Carl Jung and the developers of the Myers–Briggs Type Indicator provide a different perspective and suggest that everyone has both an extraverted side and an introverted side, with one being more dominant than the other.
Rather than focusing on interpersonal behavior, Jung defined introversion as an "attitude-type characterised by orientation in life through subjective psychic contents" and extraversion as "an attitude type characterised by concentration of interest on the external object". Extraversion is the state of obtaining gratification from outside oneself. Extraverts tend to enjoy human interactions and to be enthusiastic, talkative and gregarious. Extraverts thrive off being around other people, they take pleasure in activities that involve large social gatherings, such as parties, community activities, public demonstrations, business or political groups. They tend to work well in groups. An extraverted person is to enjoy time spent with people and find less reward in time spent alone, they tend to be energized when around other people, they are more prone to boredom when they are by themselves. Introversion is the state of being predominantly interested in one's own mental self. Introverts are perceived as more reserved or reflective.
Some popular psychologists have characterized introverts as people whose energy tends to expand through reflection and dwindle during interaction. This is similar to Jung's view. Few modern conceptions make this distinction. Introverts take pleasure in solitary activities such as reading, using computers, hiking, or fishing; the archetypal artist, sculptor, engineer and inventor are all introverted. An introvert is to enjoy time spent alone and find less reward in time spent with large groups of people, though they may enjoy interactions with close friends. Trust is an issue of significance: a virtue of utmost importance to introverts is choosing a worthy companion, they prefer to concentrate on a single activity at a time and like to observe situations before they participate observed in developing children and adolescents. They are more analytical before speaking. Introverts are overwhelmed by too much stimulation from social gatherings and engagement, introversion having been defined by some in terms of a preference for a quiet, more minimally stimulating external environment.
Mistaking introversion for shyness is a common error. Introversion is a preference. Introverts prefer solitary to social activities, but do not fear social encounters like shy people do. Susan Cain argues that modern Western culture misjudges the capabilities of introverted people, leading to a waste of talent and happiness. Cain describes how society is biased against introverts, that, with people being taught from childhood that to be sociable is to be happy, introversion is now considered "somewhere between a disappointment and pathology". In contrast, Cain says that introversion is not a "second-class" trait but that both introverts and extraverts enrich society, with examples including the introverts J. K. Rowling, Isaac Newton, Albert Einstein, Mahatma Gandhi, Dr. Seuss, W. B. Yeats, Steven Spielberg and Larry Page. Although many people view being introverted or extraverted as mutually exclusive, most contemporary trait theories measure levels of extraversion-introversion as part of a single, continuous dimension of personality, with some scores near one end, others near the half-way mark.
Ambiversion is falling less directly in the middle. An ambivert is moderately comfortable with groups and social interaction, but relishes time alone, away from a crowd. In simpler words, an ambivert is a person whose behaviour changes according to the situation they are in. In face of authority or in presence of strangers, the person may be introverted. However, in the presence of family or close friends, the person may be energetic or extraverted. Susan Cain's 2012 book Quiet: The Power of Introverts in a World That Can't Stop Talking reports that studies indicate 33–50% of the American population are introverts. Particular subpopulations have higher prevalence, with a 6000-subject MBTI-based survey indicating that 60% of attorneys, 90% of intellectual property attorneys, are introverts; the extent of extraversion and introversion is most assessed through self-report measures, although peer-reports and third-party observation can be used. Self-report measures are either lexical or based on statements.
The type of measure is determined by an assessment of psychometric properties and the time and space constraints of the research being undertaken. Lexical measures use individual adjectives that refl
The locus coeruleus is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system; the locus coeruleus is the principal site for brain synthesis of norepinephrine. The locus coeruleus and the areas of the body affected by the norepinephrine it produces are described collectively as the locus coeruleus-noradrenergic system or LC-NA system. Norepinephrine may be released directly into the blood from the adrenal medulla; the locus coeruleus is located in the posterior area of the rostral pons in the lateral floor of the fourth ventricle. It is composed of medium-size neurons. Melanin granules inside the neurons of the LC contribute to its blue colour. Thus, it is known as the nucleus pigmentosus pontis, meaning "heavily pigmented nucleus of the pons." The neuromelanin is formed by the polymerization of noradrenaline and is analogous to the black dopamine-based neuromelanin in the substantia nigra. In adult humans the locus coeruleus has 22,000 to 51,000 total pigmented neurons that range in size between 31,000 and 60,000 μm3.
The projections of this nucleus reach wide. For example, they innervate the spinal cord, the brain stem, hypothalamus, the thalamic relay nuclei, the amygdala, the basal telencephalon, the cortex; the norepinephrine from the LC has an excitatory effect on most of the brain, mediating arousal and priming the brain’s neurons to be activated by stimuli. As an important homeostatic control center of the body, the locus coeruleus receives afferents from the hypothalamus; the cingulate gyrus and the amygdala innervate the LC, allowing emotional pain and stressors to trigger noradrenergic responses. The cerebellum and afferents from the raphe nuclei project to the LC, in particular the pontine raphe nucleus and dorsal raphe nucleus; the locus coeruleus receives inputs from a number of other brain regions, primarily: The Medial prefrontal cortex, whose connection is constant and increases in strength with raised activity levels in the subject The Nucleus paragigantocellularis, which integrates autonomic and environmental stimuli The Nucleus prepositus, involved in gaze The Lateral hypothalamus, which releases orexin, which, as well as its other functions, is excitatory in the locus coeruleus.
The projections from the locus coeruleus consist of neurons that utilize norepinephrine as their primary neurotransmitter. These projections include the following connections: LC → Amygdala & Hippocampus LC → Brain stem & Spinal cord LC → Cerebellum LC → Cerebral cortex LC → Hypothalamus LC → Tectum LC → Thalamus LC → Ventral tegmental area It is related to many functions via its widespread projections; the LC-NA system modulates cortical, cerebellar and spinal cord circuits. Some of the most important functions influenced by this system are: Arousal and sleep-wake cycle Attention and memory Behavioral flexibility, behavioral inhibition and stress Cognitive control Emotions Neuroplasticity Posture and balanceThe locus coeruleus is a part of the reticular activating system, is completely inactivated in rapid eye movement sleep; the locus coeruleus may figure in clinical depression, panic disorder, Parkinson's disease, Alzheimer's disease and anxiety. Some medications including norepinephrine reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors are believed to show efficacy by acting upon neurons in this area.
Research continues to reveal that norepinephrine is a critical regulator of numerous activities from stress response, the formation of memory to attention and arousal. Many neuropsychiatric disorders precipitate from alterations to NE modulated neurocircuitry: disorders of affect, anxiety disorders, PTSD, ADHD and Alzheimer’s disease. Alterations in the locus coeruleus accompany dysregulation of NE function and play a key role in the pathophysiology of these neuropsychiatric disorders; the locus coeruleus is responsible for mediating many of the sympathetic effects during stress. The locus coeruleus is activated by stress, will respond by increasing norepinephrine secretion, which in turn will alter cognitive function, increase motivation, activate the hypothalamic-pituitary-adrenal axis, increase the sympathetic discharge/inhibit parasympathetic tone. Specific to the activation of the hypothalamo-pituitary adrenal axis, norepinephrine will stimulate the secretion of corticotropin-releasing factor from the hypothalamus, that induces adrenocorticotropic hormone release from the anterior pituitary and subsequent cortisol synthesis in the adrenal glands.
Norepinephrine released from locus coeruleus will feedback to inhibit its production, corticotropin-releasing hormone will feedback to inhibit its production, while positively feeding to the locus coeruleus to increase norepinephrine production. The LC's role in cognitive function in relation to stress is multi-modal. Norepinephrine released from the LC can act on α2 receptors to increase working memory, or an excess of NE may decrease working memory by binding to the lower-affinity α1 receptors. Psychiatric research has documented that enhanced noradrenergic postsynaptic responsiveness in the neuronal pathway that originates in the locus coeruleus and ends in the basolateral nucleus of the amygdala is a major factor in the pathophysiology of most stress-induced fear-circuitry disorders and in posttraumatic stress disorder; the LC neurons are probabl
G protein-coupled receptor
G protein-coupled receptors known as seven--transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, G protein–linked receptors, constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, animals; the ligands that bind and activate these receptors include light-sensitive compounds, pheromones and neurotransmitters, vary in size from small molecules to peptides to large proteins. G protein-coupled receptors are involved in many diseases, are the target of 34% of all modern medicinal drugs. There are two principal signal transduction pathways involving the G protein-coupled receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway.
When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor. The GPCR can activate an associated G protein by exchanging the GDP bound to the G protein for a GTP; the G protein's α subunit, together with the bound GTP, can dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type. GPCRs are an important drug target and 34% of all Food and Drug Administration approved drugs target 108 members of this family; the global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018. The 2012 Nobel Prize in Chemistry was awarded to Brian Kobilka and Robert Lefkowitz for their work, "crucial for understanding how G protein-coupled receptors function". There have been at least seven other Nobel Prizes awarded for some aspect of G protein–mediated signaling; as of 2012, two of the top ten global best-selling drugs act by targeting G protein-coupled receptors.
The exact size of the GPCR superfamily is unknown, but at least 810 different human genes have been predicted to code for them from genome sequence analysis. Although numerous classification schemes have been proposed, the superfamily was classically divided into three main classes with no detectable shared sequence homology between classes; the largest class by far is class A. Of class A GPCRs, over half of these are predicted to encode olfactory receptors, while the remaining receptors are liganded by known endogenous compounds or are classified as orphan receptors. Despite the lack of sequence homology between classes, all GPCRs have a common structure and mechanism of signal transduction; the large rhodopsin A group has been further subdivided into 19 subgroups. According to the classical A-F system, GPCRs can be grouped into 6 classes based on sequence homology and functional similarity: Class A Class B Class C Class D Class E Class F More an alternative classification system called GRAFS has been proposed for vertebrate GPCRs.
They correspond to classical classes C, A, B2, F, B. An early study based on available DNA sequence suggested that the human genome encodes 750 G protein-coupled receptors, about 350 of which detect hormones, growth factors, other endogenous ligands. 150 of the GPCRs found in the human genome have unknown functions. Some web-servers and bioinformatics prediction methods have been used for predicting the classification of GPCRs according to their amino acid sequence alone, by means of the pseudo amino acid composition approach. GPCRs are involved in a wide variety of physiological processes; some examples of their physiological roles include: The visual sense: The opsins evolved from early GPCRs over 650 million years ago, use a photoisomerization reaction to translate electromagnetic radiation into cellular signals. Rhodopsin, for example, uses the conversion of 11-cis-retinal to all-trans-retinal for this purpose; the gustatory sense: GPCRs in taste cells mediate release of gustducin in response to bitter-, umami- and sweet-tasting substances.
The sense of smell: Receptors of the olfactory epithelium bind odorants and pheromones Behavioral and mood regulation: Receptors in the mammalian brain bind several different neurotransmitters, including serotonin, dopamine, GABA, glutamate Regulation of immune system activity and inflammation: Chemokine receptors bind ligands that mediate intercellular communication between cells of the immune system. GPCRs are involved in immune-modulation and directly involved in suppression of TLR-induced immune responses from T cells. Autonomic nervous system transmission: Both the sympathetic and parasympathetic nervous systems are regulated by GPCR pathways, responsible for control of many automatic functions of the body such as blood pressure, heart rate, digestive processes Cell density sensing: A novel GPCR role in regulating cell density sensing. Homeostasis modulation. Involved in growth and metastasis of some types of tumors. Used in the endocrine syste
In neuroanatomy, the cingulum is a collection of white matter, fibers projecting from the cingulate gyrus to the entorhinal cortex in the brain, allowing for communication between components of the limbic system. It forms the white matter core of the cingulate gyrus, following it from the subcallosal gyrus of the frontal lobe beneath the rostrum of corpus callosum to the parahippocampal gyrus and uncus of the temporal lobe. Neurons of the cingulum receive afferent fibers from the parts of the thalamus that are associated with the spinothalamic tract. This, in addition to the fact that the cingulum is a central structure in learning to correct mistakes, indicates that the cingulum is involved in appraisal of pain and reinforcement of behavior that reduces it. Cingulotomy, the surgical severing of the anterior cingulum, is a form of psychosurgery used to treat depression and OCD; the cingulum was one of the earliest identified brain structures. The cingulum is described from various brain images as a C shaped structure within the brain that wraps around the frontal lobe to the temporal lobe right above the corpus callosum.
It is located beneath the cingulate gyrus within the medial surface of the brain therefore encircling the entire brain. There are two primary parts of the cingulate cortex: the posterior cingulate cortex and the anterior cingulate cortex; the anterior is linked to emotion apathy and depression. Here function and structure changes are related meaning any change within this structure would lead to a function change behavioral because of its function involving emotions. Damage to this area can have various effects on mental health; the posterior section is more related to cognitive functions. This can include attention and spatial skills, working memory and general memory; because of its location, the cingulum is important to brain structure connectivity and the integration of information that it receives. In recent years the cingulum has been associated with various brain diseases. One such area of interest is the disruption of white matter in the posterior cingulum causing mild cognitive impairment.
Using diffusion MRI techniques, researchers have associated mild cognitive impairment with damage to the cingulum. The cingulum is a frontal association tract that could play a critical role because it connects sites implicated in cognitive control; the middle segment of the cingulum contains connections with motor cortical areas. Another place of importance that explains the cingulum and its relation to mild cognitive impairment is the fact that the cingulum connects to the hippocampus; the cingulum integrates this to other parts of the brain. Damage to the cingulum simultaneously damages the hippocampus; this is vital. Damage to gray matter, bodies of neurons, or white matter of axons in the cingulum therefore can affect humans cognitively because of this damage. Variations in microstructure of a group of fibers in the rostral cingulum have been shown to be sensitive to performance of cognitive control tasks. White matter pathology of the cingulum represents one of the earliest changes in development of age-related dementia and is aiding researchers worldwide to discover more about this relationship.
Cingulate Gyrus: Introduction and Surface Morphology
Dopamine is an organic chemical of the catecholamine and phenethylamine families. It functions both as a hormone and a neurotransmitter, plays several important roles in the brain and body, it is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical L-DOPA, synthesized in the brain and kidneys. Dopamine is synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells; the brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones; these pathways and cell groups form a dopamine system, neuromodulatory.
In popular culture and media, dopamine is seen as the main chemical of pleasure, but the current opinion in pharmacology is that dopamine instead confers motivational salience. Outside the central nervous system, dopamine functions as a local paracrine messenger. In blood vessels, it acts as a vasodilator. With the exception of the blood vessels, dopamine in each of these peripheral systems is synthesized locally and exerts its effects near the cells that release it. Several important diseases of the nervous system are associated with dysfunctions of the dopamine system, some of the key medications used to treat them work by altering the effects of dopamine. Parkinson's disease, a degenerative condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra, its metabolic precursor L-DOPA can be manufactured. There is evidence that schizophrenia involves altered levels of dopamine activity, most antipsychotic drugs used to treat this are dopamine antagonists which reduce dopamine activity.
Similar dopamine antagonist drugs are some of the most effective anti-nausea agents. Restless legs syndrome and attention deficit hyperactivity disorder are associated with decreased dopamine activity. Dopaminergic stimulants can be addictive in high doses, but some are used at lower doses to treat ADHD. Dopamine itself is available as a manufactured medication for intravenous injection: although it cannot reach the brain from the bloodstream, its peripheral effects make it useful in the treatment of heart failure or shock in newborn babies. A dopamine molecule consists of a catechol structure with one amine group attached via an ethyl chain; as such, dopamine is the simplest possible catecholamine, a family that includes the neurotransmitters norepinephrine and epinephrine. The presence of a benzene ring with this amine attachment makes it a substituted phenethylamine, a family that includes numerous psychoactive drugs. Like most amines, dopamine is an organic base; as a base, it is protonated in acidic environments.
The protonated form is water-soluble and stable, but can become oxidized if exposed to oxygen or other oxidants. In basic environments, dopamine is not protonated. In this free base form, it is less water-soluble and more reactive; because of the increased stability and water-solubility of the protonated form, dopamine is supplied for chemical or pharmaceutical use as dopamine hydrochloride—that is, the hydrochloride salt, created when dopamine is combined with hydrochloric acid. In dry form, dopamine hydrochloride is a fine colorless powder. Dopamine is synthesized in a restricted set of cell types neurons and cells in the medulla of the adrenal glands; the primary and minor metabolic pathways are: Primary: L-Phenylalanine → L-Tyrosine → L-DOPA → Dopamine Minor: L-Phenylalanine → L-Tyrosine → p-Tyramine → Dopamine Minor: L-Phenylalanine → m-Tyrosine → m-Tyramine → DopamineThe direct precursor of dopamine, L-DOPA, can be synthesized indirectly from the essential amino acid phenylalanine or directly from the non-essential amino acid tyrosine.
These amino acids are found in nearly every protein and so are available in food, with tyrosine being the most common. Although dopamine is found in many types of food, it is incapable of crossing the blood–brain barrier that surrounds and protects the brain, it must therefore be synthesized inside the brain to perform its neuronal activity. L-Phenylalanine is converted into L-tyrosine by the enzyme phenylalanine hydroxylase, with molecular oxygen and tetrahydrobiopterin as cofactors. L-Tyrosine is converted into L-DOPA by the enzyme tyrosine hydroxylase, with tetrahydrobiopterin, O2, iron as cofactors. L-DOPA is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase, with pyridoxal phosphate as the cofactor. Dopamine itself is used as precursor in the synthesis o
Neurotransmitters are endogenous chemicals that enable neurotransmission. It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron to another "target" neuron, muscle cell, or gland cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are available from the diet and only require a small number of biosynthetic steps for conversion. Neurotransmitters play a major role in shaping everyday life and functions, their exact numbers are unknown, but more than 200 chemical messengers have been uniquely identified. Neurotransmitters are stored in synaptic vesicles, clustered close to the cell membrane at the axon terminal of the presynaptic neuron. Neurotransmitters are released into and diffuse across the synaptic cleft, where they bind to specific receptors on the membrane of the postsynaptic neuron.
Most neurotransmitters are about the size of a single amino acid. A released neurotransmitter is available in the synaptic cleft for a short time before it is metabolized by enzymes, pulled back into the presynaptic neuron through reuptake, or bound to a postsynaptic receptor. Short-term exposure of the receptor to a neurotransmitter is sufficient for causing a postsynaptic response by way of synaptic transmission. In response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. Low level "baseline" release occurs without electrical stimulation; the released neurotransmitter may move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way; this neuron may be connected to many more neurons, if the total of excitatory influences are greater than those of inhibitory influences, the neuron will "fire".
It will create a new action potential at its axon hillock to release neurotransmitters and pass on the information to yet another neighboring neuron. Until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through the careful histological examinations by Ramón y Cajal, a 20 to 40 nm gap between neurons, known today as the synaptic cleft, was discovered; the presence of such a gap suggested communication via chemical messengers traversing the synaptic cleft, in 1921 German pharmacologist Otto Loewi confirmed that neurons can communicate by releasing chemicals. Through a series of experiments involving the vagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs by controlling the amount of saline solution present around the vagus nerve. Upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine —the first known neurotransmitter.
Some neurons do, communicate via electrical synapses through the use of gap junctions, which allow specific ions to pass directly from one cell to another. There are four main criteria for identifying neurotransmitters: The chemical must be synthesized in the neuron or otherwise be present in it; when the neuron is active, the chemical must produce a response in some target. The same response must be obtained. A mechanism must exist for removing the chemical from its site of activation. However, given advances in pharmacology and chemical neuroanatomy, the term "neurotransmitter" can be applied to chemicals that: Carry messages between neurons via influence on the postsynaptic membrane. Have little or no effect on membrane voltage, but have a common carrying function such as changing the structure of the synapse. Communicate by sending reverse-direction messages that affect the release or reuptake of transmitters; the anatomical localization of neurotransmitters is determined using immunocytochemical techniques, which identify the location of either the transmitter substances themselves, or of the enzymes that are involved in their synthesis.
Immunocytochemical techniques have revealed that many transmitters the neuropeptides, are co-localized, that is, one neuron may release more than one transmitter from its synaptic terminal. Various techniques and experiments such as staining and collecting can be used to identify neurotransmitters throughout the central nervous system. There are many different ways. Dividing them into amino acids and monoamines is sufficient for some classification purposes. Major neurotransmitters: Amino acids: glutamate, aspartate, D-serine, γ-aminobutyric acid, glycine Gasotransmitters: nitric oxide, carbon monoxide, hydrogen sulfide Monoamines: dopamine, epinephrine, serotonin Trace amines: phenethylamine, N-methylphenethylamine, tyramine, 3-iodothyronamine, tryptamine, etc. Peptides: oxytocin, substance P, cocaine and amphetamine regulated transcript, opioid peptides Purines: adenosine triphosphate, adenosine Catecholamines: dopamine, epinephrine Others: acetylcholine, etc. In addition, over 50 neuroactive pepti
Glutamic acid is an α-amino acid, used by all living beings in the biosynthesis of proteins. It is non-essential in humans, it is an excitatory neurotransmitter, in fact the most abundant one, in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid in GABA-ergic neurons, it has a formula C5H9O4N. Its molecular structure could be idealized as HOOC-CH-2-COOH, with two carboxyl groups -COOH and one amino group -NH2. However, in the solid state and mildly acid water solutions, the molecule assumes an electrically neutral zwitterion structure −OOC-CH-2-COOH, it is encoded by the codons GAA or GAG. The acid can lose one proton from its second carboxyl group to form the conjugate base, the singly-negative anion glutamate −OOC-CH-2-COO−; this form of the compound is prevalent in neutral solutions. The glutamate neurotransmitter plays the principal role in neural activation; this anion is responsible for the savory flavor of certain foods, used in glutamate flavorings such as MSG.
In Europe it is classified as food additive E620. In alkaline solutions the doubly negative anion −OOC-CH-2-COO− prevails; the radical corresponding to glutamate is called glutamyl. When glutamic acid is dissolved in water, the amino group may gain a proton, and/or the carboxyl groups may lose protons, depending on the acidity of the medium. In sufficiently acidic environments, the amino group gains a proton and the molecule becomes a cation with a single positive charge, HOOC-CH-2-COOH. At pH values between about 2.5 and 4.1, the carboxylic acid closer to the amine loses a proton, the acid becomes the neutral zwitterion −OOC-CH-2-COOH. This is the form of the compound in the crystalline solid state; the change in protonation state is gradual. At higher pH, the other carboxylic acid group loses its proton and the acid exists entirely as the glutamate anion −OOC-CH-2-COO−, with a single negative charge overall; the change in protonation state occurs at pH 4.07. This form with both carboxylates lacking protons is dominant in the physiological pH range.
At higher pH, the amino group loses the extra proton and the prevalent species is the doubly-negative anion −OOC-CH-2-COO−. The change in protonation state occurs at pH 9.47. The carbon atom adjacent to the amino group is chiral, so glutamic acid can exist in two optical isomers, D and L; the L form is the one most occurring in nature, but the D form occurs in some special contexts, such as the cell walls of the bacteria and the liver of mammals. Although they occur in many foods, the flavor contributions made by glutamic acid and other amino acids were only scientifically identified early in the twentieth century; the substance was discovered and identified in the year 1866, by the German chemist Karl Heinrich Ritthausen who treated wheat gluten with sulfuric acid. In 1908 Japanese researcher Kikunae Ikeda of the Tokyo Imperial University identified brown crystals left behind after the evaporation of a large amount of kombu broth as glutamic acid; these crystals, when tasted, reproduced the ineffable but undeniable flavor he detected in many foods, most in seaweed.
Professor Ikeda termed this flavor umami. He patented a method of mass-producing a crystalline salt of glutamic acid, monosodium glutamate. Glutamic acid is produced on the largest scale of any amino acid, with an estimated annual production of about 1.5 million tons in 2006. Chemical synthesis was supplanted by the aerobic fermentation of sugars and ammonia in the 1950s, with the organism Corynebacterium glutamicum being the most used for production. Isolation and purification can be achieved by crystallization. Glutamate is a key compound in cellular metabolism. In humans, dietary proteins are broken down by digestion into amino acids, which serve as metabolic fuel for other functional roles in the body. A key process in amino acid degradation is transamination, in which the amino group of an amino acid is transferred to an α-ketoacid catalysed by a transaminase; the reaction can be generalised as such: R1-amino acid + R2-α-ketoacid ⇌ R1-α-ketoacid + R2-amino acidA common α-keto acid is α-ketoglutarate, an intermediate in the citric acid cycle.
Transamination of α-ketoglutarate gives glutamate. The resulting α-ketoacid product is a useful one as well, which can contribute as fuel or as a substrate for further metabolism processes. Examples are as follows: Alanine + α-ketoglutarate ⇌ pyruvate + glutamateAspartate + α-ketoglutarate ⇌ oxaloacetate + glutamateBoth pyruvate and oxaloacetate are key components of cellular metabolism, contributing as substrates or intermediates in fundamental processes such as glycolysis and the citric acid cycle. Glutamate plays an important role in the body's disposal of excess or waste nitrogen. Glutamate undergoes deamination, an oxidative reaction catalysed by glutamate dehydrogenase, as follows: glutamate + H2O + NADP+ → α-ketoglutarate + NADPH + NH3 + H+Ammonia is excreted predominantly as urea, synthesised in the liver. Transamination can thus be linked to deamination allowing nitrogen from the amine groups of amino acids to be removed, via glutamate as an intermediate, excreted from the body in the form of urea.
Glutamate is a