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GLYCINE
Presented by A. Gowtham Sashtha 1st M.Pharm
Department of pharmacology
K.M College of pharmacy.
Madurai – 625107.
Introduction
➜ Glycine is smallest amino acids and acts as a inhibitory neuronal transmission
➜ Glycine is a colorless, sweet-tasting crystalline solid.
➜ Glycine distributed in body fluids and tissue proteins.
and it's structurally and functionally similar to the GABAa receptor.
➜ Glycine is present in particularly high concentration
(5 µmol/g) in the grey matter of the spinal cord.
➜structure :
Function
➜There, they are mainly involved in motor control and pain
perception in the adult.
➜To prevent the tissue injury.
➜To enhance the anti-oxidants capacity.
➜To promote protein synthesis and wound healing.
➜To improve immunity.
➜To improve digestion and glucose control.
➜Synthesis
➜Storage & Release
➜Binding & Receptors
➜Metabolism
➜Reuptake
➜Glycine Receptor Agonists
➜Glycine Receptor Antagonist
➜Metabolic disorders of Glycine
Biosynthesis of glycine
Glycine synthesized by 4 steps
➜From serine
➜From Threonine
➜From CO2 & NH3
➜From Glyoxalate
Storage & Release
GABA, glycine, and glutamate are the only major amino acid neurotransmitters
stored in synaptic vesicles (VIAT)and that GABA and glycine are transported by
similar, if not identical transporters.
Binding & Receptors
Glycine binding with both α & β subtypes receptors.
It is ligand gated ion channel types of receptors and also knowns as inhibitory
chloride channel protein.
Glycine Receptors are Closely Related to GABAa Receptors.
Glycine receptors are the major inhibitory receptors in the spinal cord and brain
stem.
It provide inhibitory functions similar to the GABAa and NMDA receptors.
Activation of NMDA & GlyR Receptors
Receptors Subtypes & its location
Glycine Receptors containing 2 subunits α & β
α-subunit (α1-4) of GlyR contain ↆ
GLRA1 - Spinal cord,Brain stem,Colliculi.
GLRA2 - Hippocampus, Cerebral cortex, Thalamus.
GLRA3 - Cerebellum, Olfactory bulb, Hippocampus.
GLRA4 - in chick : Embryonic spinal cord, sensory, sympathetic ganglia.
β-Subunit contain ↆ
GLYRB - Throughout the embryonic and adult CNS.
also involved in GABAa and NMDA receptors.
Metabolism
of
Glycine
Reuptake
Glycine is rapidly reuptake into the
presynaptic terminal or surrounding glial
cells with help of two glycine
transporters, GLYT1 and GLYT2, are
known.
Inhibited by Bitopertin, Sarcosine
selective glycine transporters blocking
agent
GlyT1 blocker : N-Arachidonylglycine
Drugs Acting on Glycine Receptors Agonist
➜Glycine
➜β-Alanine
➜L-Alanine
➜D-Serine & L-Serine
➜Taurine
➜Hypotaurine
➜Milacemide
Glycine
➜Glycine available in tablet & injection form.
➜Rich foods including meat, fish, dairy, and legumes. Glycine can also be
taken as a supplement.
➜Some researchers think glycine may have a role in cancer prevention
because it seems to interfere with the blood supply needed by certain tumors.
use : Glycine is used for treating schizophrenia, stroke, benign prostatic
hyperplasia (BPH), It is also used to protect kidneys from the harmful side
effects of certain drugs used after organ transplantation as well as the liver
from harmful effects of alcohol.
β-Alanine & L-Alanine
Beta-alanine That's a compound produced in muscle endurance in
high-intensity exercise. is commonly used by mouth for improving athletic
performance and building lean muscle mass in younger adults, and
improving physical performance in elderly adults.
Alpha-alanine It is produced from pyruvate by transamination. is used for
low blood sugar (hypoglycemia), diarrhea-related dehydration, liver disease,
enlarged prostate (benign prostatic hypertrophy, BPH), fatigue, stress, and
certain inherited disorders including glycogen storage disease and urea
cycle disorders.
D-Serine & l-Serine
D-serine is a potent co-agonist at the NMDA glutamate receptor . used for
schizophrenia, Parkinson disease, and memory and thinking skills (cognitive
function),
L-serine The conversion of L-serine to glycine by serine
hydroxymethyltransferase results in the formation of the one-carbon units
necessary for the synthesis of the purine bases, adenine and guanine.is
used to improve sleeping, Lou Gehrig's disease
ADR : Nausea, vomiting, and stomach upset,
Taurine & Hypotaurine
Taurine Taurine activates glycine receptors to mediate its effects on
neurons.occurs naturally in the human brain.Taurine is an herbal
supplement that can be used in the treatment for congestive heart failure,
high blood pressure, high cholesterol, cystic fibrosis, and to prevent the
buildup of plaque in the arteries throughout the body.
Hypotaurine is a biosynthesis of taurine. it also acts as an endogenous
neurotransmitter via action on the glycine receptors. It is an osmolyte with
antioxidant properties.
ADR : diarrhea and constipation.
Milacemide
Milacemide (INN) it's a glycine prodrug. directly acting on Glycine
Receptors. It has been studied for its effects on human memory and as a
potential treatment for the symptoms of Alzheimer's disease. and also act
as MAO-B Inhibitors.
Drug Acting on Glycine Receptors Antagonist
Selective.
➜Strychnine.
➜Brucine.
➜Tutin.
Non-selective.
➜Bicuculline.
➜Caffeine. ➜Pitrazepin.
➜Picrotoxin. ➜Thiocolchicoside.
Strychnine
Strychnine It primarily affects the motor nerve fibers in the spinal cord
which control muscle contraction. that can be taken by mouth, inhaled
(breathed in), or mixed in a solution and given intravenously. only is a small
amount needed to the patient.
ADR : Agitation,fear,Restlessness.,Easily startled,Jaw tightness
use : It is used in veterinary medicine as CNS stimulant and tonic and
Strychnine causes muscular convulsions
It is used to antidote for barbiturates poisoning & also used for
rodenticide.
Brucine
Brucine closely related to strychnine.
ADR : muscle spasms, convulsions, rhabdomyolysis, and acute kidney
injury.
use :It is used in anti-inflammatory and analgesic agent, as well as in
some Ayurveda and homeopathy drugs.
Tetanus toxin
Tetanus toxin blocks the release of the inhibitory neurotransmitters
glycine and GABA.
Tetanus toxin produced by the vegetative cell of Clostridium tetani in
anaerobic conditions caused by tetanus.
Tetanus toxin does not cross to the blood brain barrier.
Tetanus toxin may bind directly at neuromuscular junctions and cause
neuromuscular facilitation.
Symptoms:
Tetanus causes painful muscle contractions, particularly in the jaw and
neck. It can interfere with the ability to breathe, eventually causing death.
Clinical manifestations :
Whole body: fever, high blood pressure, nervous system
dysfunction, or sweating
Muscular: muscle spasms, cramping, facial muscle spasms, or stiff
muscles
Respiratory: episodes of no breathing or shortness of breath
Treatment :
Antibiotic, penicillin, sedative drugs, Dietary supplements.
Tetanus toxoid vaccine.
Bicuculline & picrotoxin
Bicuculline acts as a competitive antagonist at the GABA-binding site of
the GABAa receptor. This model can be used for screening for classical
anticonvulsant drugs,
Picrotoxin It is a noncompetitive antagonist at GABAA receptors & acts as
inhibitory chloride ion channel in GABAa receptors and it is used as a CNS
stimulant, antidote, convulsant,
ADR : unconsciousness, delirium, convulsions, gastro-enteritis and
stimulation of the respiratory centre followed by paralysis, from which
death sometimes results.
Coffeine
Caffeine is a weak competitive glycine antagonist, with slightly differing
IC50 at the four GlyR subtypes. GlyR subtypes have differing caffeine
sensitivity. and it effectively suppress the glycine GlyR subtypes.
ADR : Dizziness, headache, Restlessness, Dehydration, anxiety.
use: Caffeine is the most widely used psychoactive drug,
Thiocolchicoside
Thiocolchicoside acts as a glycine receptors antagonist and also act as a
competitive GABAa receptor antagonist with similar potency.and nicotinic
acetylcholine receptors to a much lesser extent.
ADR : Nausea, vomiting, diarrhoea,skin rashes, itching, Drowsiness
use: muscle relaxant with anti-inflammatory analgesic effects spinal cord
disorder and relieve pain after surgery.
Glycine site blocking drug
Kynurenic acid : This drug acting as an
antagonist at excitatory amino acid receptors.
for example NMDA receptors.
This drug is used to antiexcitotoxic and
anticonvulsant
Metabolic disorder of glycine
1) Hyperekplexia (Startle disease)
Hyperekplexia is a rare hereditary, neurological disorder that may
affect infants as newborns (neonatal) or prior to birth (in utero). It may also
affect children and adults.
Individuals with this disorder have an excessive startle reaction (eye
blinking or body spasms) to sudden unexpected noise, movement, or touch.
It is treated by administration of the drug is clonazepam.
2) Glycinuria :
Glycine level increased in blood and CSF. It is a rare disorder. kidney
disorder characterized by the presence of excessive amounts of glycine in
the urine but serum glycine is normal.
It is characterized by increased formation of oxalate renal stone.
Symptoms : encephalopathy, mental retardation, deafness, blindness,
kidney stones, hypertension
Treatment :
⇑ - Water intake - Increases oxalate excretion in urine.
⇓ - oxalate in diet - spinach,beet-root,tea,sesame seeds.
3) Hyperoxaluria :
It is a condition that occurs when there is too much oxalate in urine
To produce kidney stones and loss of kidney function..
It is normally eliminated from the body through the kidneys in the
urine (and can also be eliminated through stool).
Symptoms : Severe or sudden back pain.Blood in the urine.Pain when
urinating.Chills or fever.
It is treated by administration of the drug is oxlumo(lumasiran)
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Everything You Need to Know About the Amino Acid Glycine

  • 1. GLYCINE Presented by A. Gowtham Sashtha 1st M.Pharm Department of pharmacology K.M College of pharmacy. Madurai – 625107.
  • 2. Introduction ➜ Glycine is smallest amino acids and acts as a inhibitory neuronal transmission ➜ Glycine is a colorless, sweet-tasting crystalline solid. ➜ Glycine distributed in body fluids and tissue proteins. and it's structurally and functionally similar to the GABAa receptor. ➜ Glycine is present in particularly high concentration (5 µmol/g) in the grey matter of the spinal cord. ➜structure :
  • 3. Function ➜There, they are mainly involved in motor control and pain perception in the adult. ➜To prevent the tissue injury. ➜To enhance the anti-oxidants capacity. ➜To promote protein synthesis and wound healing. ➜To improve immunity. ➜To improve digestion and glucose control.
  • 4. ➜Synthesis ➜Storage & Release ➜Binding & Receptors ➜Metabolism ➜Reuptake ➜Glycine Receptor Agonists ➜Glycine Receptor Antagonist ➜Metabolic disorders of Glycine
  • 5.
  • 6. Biosynthesis of glycine Glycine synthesized by 4 steps ➜From serine ➜From Threonine ➜From CO2 & NH3 ➜From Glyoxalate
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  • 11. Storage & Release GABA, glycine, and glutamate are the only major amino acid neurotransmitters stored in synaptic vesicles (VIAT)and that GABA and glycine are transported by similar, if not identical transporters. Binding & Receptors Glycine binding with both α & β subtypes receptors. It is ligand gated ion channel types of receptors and also knowns as inhibitory chloride channel protein. Glycine Receptors are Closely Related to GABAa Receptors. Glycine receptors are the major inhibitory receptors in the spinal cord and brain stem. It provide inhibitory functions similar to the GABAa and NMDA receptors.
  • 12. Activation of NMDA & GlyR Receptors
  • 13. Receptors Subtypes & its location Glycine Receptors containing 2 subunits α & β α-subunit (α1-4) of GlyR contain ↆ GLRA1 - Spinal cord,Brain stem,Colliculi. GLRA2 - Hippocampus, Cerebral cortex, Thalamus. GLRA3 - Cerebellum, Olfactory bulb, Hippocampus. GLRA4 - in chick : Embryonic spinal cord, sensory, sympathetic ganglia. β-Subunit contain ↆ GLYRB - Throughout the embryonic and adult CNS. also involved in GABAa and NMDA receptors.
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  • 20. Reuptake Glycine is rapidly reuptake into the presynaptic terminal or surrounding glial cells with help of two glycine transporters, GLYT1 and GLYT2, are known. Inhibited by Bitopertin, Sarcosine selective glycine transporters blocking agent GlyT1 blocker : N-Arachidonylglycine
  • 21. Drugs Acting on Glycine Receptors Agonist ➜Glycine ➜β-Alanine ➜L-Alanine ➜D-Serine & L-Serine ➜Taurine ➜Hypotaurine ➜Milacemide
  • 22. Glycine ➜Glycine available in tablet & injection form. ➜Rich foods including meat, fish, dairy, and legumes. Glycine can also be taken as a supplement. ➜Some researchers think glycine may have a role in cancer prevention because it seems to interfere with the blood supply needed by certain tumors. use : Glycine is used for treating schizophrenia, stroke, benign prostatic hyperplasia (BPH), It is also used to protect kidneys from the harmful side effects of certain drugs used after organ transplantation as well as the liver from harmful effects of alcohol.
  • 23. β-Alanine & L-Alanine Beta-alanine That's a compound produced in muscle endurance in high-intensity exercise. is commonly used by mouth for improving athletic performance and building lean muscle mass in younger adults, and improving physical performance in elderly adults. Alpha-alanine It is produced from pyruvate by transamination. is used for low blood sugar (hypoglycemia), diarrhea-related dehydration, liver disease, enlarged prostate (benign prostatic hypertrophy, BPH), fatigue, stress, and certain inherited disorders including glycogen storage disease and urea cycle disorders.
  • 24. D-Serine & l-Serine D-serine is a potent co-agonist at the NMDA glutamate receptor . used for schizophrenia, Parkinson disease, and memory and thinking skills (cognitive function), L-serine The conversion of L-serine to glycine by serine hydroxymethyltransferase results in the formation of the one-carbon units necessary for the synthesis of the purine bases, adenine and guanine.is used to improve sleeping, Lou Gehrig's disease ADR : Nausea, vomiting, and stomach upset,
  • 25. Taurine & Hypotaurine Taurine Taurine activates glycine receptors to mediate its effects on neurons.occurs naturally in the human brain.Taurine is an herbal supplement that can be used in the treatment for congestive heart failure, high blood pressure, high cholesterol, cystic fibrosis, and to prevent the buildup of plaque in the arteries throughout the body. Hypotaurine is a biosynthesis of taurine. it also acts as an endogenous neurotransmitter via action on the glycine receptors. It is an osmolyte with antioxidant properties. ADR : diarrhea and constipation.
  • 26. Milacemide Milacemide (INN) it's a glycine prodrug. directly acting on Glycine Receptors. It has been studied for its effects on human memory and as a potential treatment for the symptoms of Alzheimer's disease. and also act as MAO-B Inhibitors.
  • 27. Drug Acting on Glycine Receptors Antagonist Selective. ➜Strychnine. ➜Brucine. ➜Tutin. Non-selective. ➜Bicuculline. ➜Caffeine. ➜Pitrazepin. ➜Picrotoxin. ➜Thiocolchicoside.
  • 28. Strychnine Strychnine It primarily affects the motor nerve fibers in the spinal cord which control muscle contraction. that can be taken by mouth, inhaled (breathed in), or mixed in a solution and given intravenously. only is a small amount needed to the patient. ADR : Agitation,fear,Restlessness.,Easily startled,Jaw tightness use : It is used in veterinary medicine as CNS stimulant and tonic and Strychnine causes muscular convulsions It is used to antidote for barbiturates poisoning & also used for rodenticide.
  • 29. Brucine Brucine closely related to strychnine. ADR : muscle spasms, convulsions, rhabdomyolysis, and acute kidney injury. use :It is used in anti-inflammatory and analgesic agent, as well as in some Ayurveda and homeopathy drugs.
  • 30. Tetanus toxin Tetanus toxin blocks the release of the inhibitory neurotransmitters glycine and GABA. Tetanus toxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions caused by tetanus. Tetanus toxin does not cross to the blood brain barrier. Tetanus toxin may bind directly at neuromuscular junctions and cause neuromuscular facilitation. Symptoms: Tetanus causes painful muscle contractions, particularly in the jaw and neck. It can interfere with the ability to breathe, eventually causing death.
  • 31. Clinical manifestations : Whole body: fever, high blood pressure, nervous system dysfunction, or sweating Muscular: muscle spasms, cramping, facial muscle spasms, or stiff muscles Respiratory: episodes of no breathing or shortness of breath Treatment : Antibiotic, penicillin, sedative drugs, Dietary supplements. Tetanus toxoid vaccine.
  • 32. Bicuculline & picrotoxin Bicuculline acts as a competitive antagonist at the GABA-binding site of the GABAa receptor. This model can be used for screening for classical anticonvulsant drugs, Picrotoxin It is a noncompetitive antagonist at GABAA receptors & acts as inhibitory chloride ion channel in GABAa receptors and it is used as a CNS stimulant, antidote, convulsant, ADR : unconsciousness, delirium, convulsions, gastro-enteritis and stimulation of the respiratory centre followed by paralysis, from which death sometimes results.
  • 33. Coffeine Caffeine is a weak competitive glycine antagonist, with slightly differing IC50 at the four GlyR subtypes. GlyR subtypes have differing caffeine sensitivity. and it effectively suppress the glycine GlyR subtypes. ADR : Dizziness, headache, Restlessness, Dehydration, anxiety. use: Caffeine is the most widely used psychoactive drug,
  • 34. Thiocolchicoside Thiocolchicoside acts as a glycine receptors antagonist and also act as a competitive GABAa receptor antagonist with similar potency.and nicotinic acetylcholine receptors to a much lesser extent. ADR : Nausea, vomiting, diarrhoea,skin rashes, itching, Drowsiness use: muscle relaxant with anti-inflammatory analgesic effects spinal cord disorder and relieve pain after surgery.
  • 35. Glycine site blocking drug Kynurenic acid : This drug acting as an antagonist at excitatory amino acid receptors. for example NMDA receptors. This drug is used to antiexcitotoxic and anticonvulsant
  • 36. Metabolic disorder of glycine 1) Hyperekplexia (Startle disease) Hyperekplexia is a rare hereditary, neurological disorder that may affect infants as newborns (neonatal) or prior to birth (in utero). It may also affect children and adults. Individuals with this disorder have an excessive startle reaction (eye blinking or body spasms) to sudden unexpected noise, movement, or touch. It is treated by administration of the drug is clonazepam.
  • 37. 2) Glycinuria : Glycine level increased in blood and CSF. It is a rare disorder. kidney disorder characterized by the presence of excessive amounts of glycine in the urine but serum glycine is normal. It is characterized by increased formation of oxalate renal stone. Symptoms : encephalopathy, mental retardation, deafness, blindness, kidney stones, hypertension Treatment : ⇑ - Water intake - Increases oxalate excretion in urine. ⇓ - oxalate in diet - spinach,beet-root,tea,sesame seeds.
  • 38. 3) Hyperoxaluria : It is a condition that occurs when there is too much oxalate in urine To produce kidney stones and loss of kidney function.. It is normally eliminated from the body through the kidneys in the urine (and can also be eliminated through stool). Symptoms : Severe or sudden back pain.Blood in the urine.Pain when urinating.Chills or fever. It is treated by administration of the drug is oxlumo(lumasiran)
  • 40. Zoho Show To create beautiful presentations, download Zoho Show from Play Store https://zoho.to/cy7 Glycine.pdf (This PDF has been generated using Zoho Show)