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Neurotransmission Associated Neurotoxicity of Monosodium Glutamate

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Monosodium Glutamate (also known as MSG) is the sodium salt of the amino acid ... (1969)Dr. John Olney (Dept. Psychiatry at Washington University St. Louis) found ... – PowerPoint PPT presentation

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Title: Neurotransmission Associated Neurotoxicity of Monosodium Glutamate


1
Neurotransmission- Associated Neurotoxicity of
Monosodium Glutamate
  • By Sarah Hardimon
  • Chem. 471

2
Introduction
  • Monosodium Glutamate (also known as MSG) is the
    sodium salt of the amino acid glutamic acid, or
    glutamate.
  • Glutamate is a normal amino acid neurotransmitter
    in the brain. (concentration around 8-12 µM)
  • At abnormally high concentrations glutamate
    glutamate is classified as an excitatory
    neurotransmitter.

3
Background
  • MSG is used as a flavor enhancer that is to make
    foods more appetizing. It has no flavor of its
    own.
  • First used in Japan. They use a sea vegetable
    (kombu) that had this flavor enhancing
    characteristic.
  • (1908) Dr. Ikeda and Dr. Suzik isolated the
    taste-enhancing chemical- glutamate. They formed
    the Ajinomoto company-MSG marketing began.

4
  • MSG hit the U.S. market around 1940, without
    testing.
  • (1969)Dr. John Olney (Dept. Psychiatry at
    Washington University St. Louis) found that MSG
    feed mice produced discrete brain lesions and
    destruction of hypothalamic nuclei.
  • Since then many MSG neuro-studies have been
    preformed. Many have proposed linking glutamate
    excitotoxicity to neurological disorders such as
    seizures, migraines, Parkinsons disease,
    Alzheimer's, etc.

5
  • Two forms of glutamate- bound (linked to
    proteins) and free. Only the free form
    enhances flavor.
  • After MSG is digested, glutamic acid is converted
    to glutamate. And when digested in the free
    form, as in MSG, the glutamate levels in the
    blood increase more significantly than when bound
    to proteins.

6
Physical Data
  • MSG fine white crystalline sold
  • Soluble in alcohol and water

7
Mechanism of Toxicity
  • Glutamate is an neurotransmitter chemical that
    allows neurons (cells) to communicate between
    each other in the brain.
  • The acute effect of glutamate is directly related
    to the immediate concentration of glutamate at
    the active site the neuron receptor- direct
    relationship of glutamate levels in the blood.
  • At high conc., neurons fire abnormally. Cells
    undergo a process of delayed cell death known as
    excitotoxicity- cells are excited to death.

8
Receptors Involved
  • Two subtypes of glutamate receptors
  • Ligand-gated (ionotropic)
  • G-protein coupled (metabotropic)
  • Ionotropic Receptors are further classified (or
    named) by their binding to specific agonist.
  • N-methly-D-aspartate receptor (NMDA Rs) is the
    only know receptor that is regulated by both
    ligand (glutamate) and by voltage.
  • NMDA Rs is the proposed site form glutamate
    toxicity.

9
Neuron
10
  • Glutamate is stored in synaptic vesicles at nerve
    terminal and are released by an action potential
    from axon.
  • Glutamate leaves the presynaptic cell
    (transmitting cell), crosses the narrow synaptic
    cleft (20 nm), and binds to the NMDA Rs on the
    postsynaptic cell (receiving cell).
  • Binding to presynaptic cell opens Ca channel,
    which is normally blocked by Mg, causing
    excitation of postsynaptic cell.

11
  • Mg is removed by a depolarization in the membrane
    potential by an influx of Na ions from voltage
    gated ion channel as a result of glutamate
    binding to NMDA- a normal cell reaction.
  • Glutamate excitation is normally terminated by
    reabsorption of glutamate across the presynaptic
    membrane.
  • However, at high conc. Calcium channels get stuck
    open leading to neural swelling and cell death.

12
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13
  • Only cells with NMDA Rs are affected
  • Neuronopathy Toxicity damages dendrites and
    neural cell bodies of the neuron. Spares the
    axons. No chance for cell regeneration.

14
  • Glutamate acts on its receptor via a nitric oxide
    mechanism. Over stimulation can lead to
    accumulation of dangerous peroxynitrite free
    radicals.
  • Ca influx results in the release of a chemical
    called arachidonic acid which cause the
    production of free radical, hydroxy radicals
  • These radical are known to bind to proteins, DAN,
    lipid membranes.

15
  • Fortunately, antioxidants (Vitamins C, E, beta
    carotene) absorb these harmful radicals.
  • However, chronic free radical exposure would
    result in an impaired functional reserve of
    antioxidant vitamins/minerals and enzymes.
  • Also, neuron utilize a great deal of energy
    (ATP), via aerobic glycolysis, in order to pump
    glutamate back into presynaptic. Any loss of
    oxygen or glucose can increase the risk of
    exitotoxic injury- Asthma, starvation,
    hypoglycemia.

16
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17
Blood Brain Barrier Issue
  • Inability of glutamate to pass through the blood
    brain barrier is one of the chief arguments for
    the proponents of MSG.
  • However, several areas of the brain are not
    protected by the blood brain barrier.
  • The hypothalamus is included in these sections of
    the brain, and where glutamate is the most
    important neurotransmitter, controls functions
    such as emotional control, caloric intake, immune
    system regulation, autonomic nervous systems,
    neuroedocrine regulation.

18
  • (1995) FDA classified MSG as a generally
    recognized as safe, or GRAS, substance.
  • The FASEB conducted a study on the safety of MSG,
    and the FDA wrote a brief summary that wrote,
    expect possibly for asthma patients, MSG was
    found to be safe by the FASEB reviewers.
  • However, there are many critics who feel that the
    FDA summary was a deception from the FASEB, which
    includes some of the FASEB reviewers.

19
  • FDA recognizes to people who may develop side
    effect
  • Those intolerant to MSG when eaten in large doses
    and those with poorly controlled asthma.
  • The FDA has proposed that any foods containing
    free glutamate must be declared on the label.
    However, there are many hidden names for both
    free and bound glutamate.
  • To avoid a major public disaster the majority of
    baby-food manufactures voluntarily stopped adding
    MSG to there products.
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