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METABOLISM OF GLYCINE
Prof (Dr)Viyatprajna Acharya
MD, PhD (Biochemistry)
OverviewofAAMetabolism
 12 out of 20 AA- synthesised from intermediates of
Glycolysis &TCA cycle
 8 AA- essential AA; what are they?
(I Love & Like To Take Potato Very Much)
 Out of 12 NEAA- 9 from amphibolic intermediates
 Rest 3 NEAA- Cys,Tyr, Hyl - from essential AA
CatabolismofAA
 Amino group- Urea
 C-skeleton- 7 products
Pyruvate
Acetyl Co-A
Acetoacetyl-CoA
α-Ketoglutarate
Succinyl Co-A
Fumarate
Oxaloacetate
Summary of catabolism of AA
Ketogenic AA– AA that are degraded to Acetyl CoA or
acetoacetylCo-A→ Ketone bodies
Lysine & Leucine- Purely ketogenic
GlucogenicAA
AA that are degraded to Pyruvate, α- ketoglutarate,
Succinyl CoA, Fumarate or Oxaloacetate
Both Ketogenic & Glucogenic AA- Phe, Tyr, Trp & Ile
INDIVIDUAL AA
GLYCINE
 Simplest AA
 Non-essential
 Glucogenic
Synthesis
1. From serine- removal of hydroxymethyl group
from Ser
2. From Threonine- byThr aldolase activity
3. By Glycine synthase system- From CO2 , NH3
& 1-C unit; reversal of Gly cleavage system
4. Aminotransferase reaction- from Glyoxylate,
Glutamate or alanine
5. From Choline
Choline
dehydrogenase Betaine
dehydrogenase
Methyltransferase
Sarcosine
demethylase
Sarcosine
oxidase
Catabolism
1. Oxidative deamination by Glycine cleavage
system- Multi-enzyme complex
1. Glycine dehydrogenase (decarboxylating)
2. Aminomethyltransferase
GLYCINE CLEAVAGE SYSTEM OF LIVER MITOCHONDRIA
2. Glucogenic pathway- first gets converted to Ser-
Reversal of serine hydroxymethyl transferase
reaction
Ser → Pyruvate
3.Biosynthesisoffollowing-
Creatine, Creatine phosphate &
Creatinine
Heme
Purine nucleotides
Glutathione
Conjugating agent
Neurotransmitter
Creatine & creatine phosphate
(MAG)
 During muscle contraction, energy is first
derived from hydrolysis of ATP
 Creatine kinase is present in – muscle, brain &
liver
 ATP regenerated by hydrolysis of creatine
phosphate- LOHMANN’S REACTION
 CK- where utilised?
 Serum Creatinine level- 0.2-1.2 mg/dl
 Creatine:
• Dietary supplement
• Used to improve athletic performance
 Creatinine:
• Urinary excretion generally constant;
 proportional to muscle mass
 Creatinine Clearance Test:
• Compares the level of Creatinine in urine (24 hrs.)
with the Creatinine level in the blood
• Used to assess kidney function
• Important determinant in dosing of several drugs
in patients with impaired renal function
Heme synthesis
Purine nucleotides
4. As a constituent of protein
Plays a vital role in protein structure- present in
turns & bends
Every 3rd AA in collagen is Glycine
GLUTATHIONE (GSH)
 Tripeptide
 Gamma-glutamyl-cysteinyl-glycine
 Widely distributed in all tissues
 GSH: GSSH (Reduced : oxidised) ratio is
maintained at 100:1 by glutathione reductase
Functionsofglutathione
 Component of antioxidant enzyme
glutathione peroxidase- scavenge free
radicals
 Maintains RBC membrane integrity. Protects
Hb from getting oxidised by H2O2
 Transport of AA- Meister cycle
 Detoxification of drugs by increasing their
solubility
 Disulfide linkages in protein structure
 Acts as a cofactor for some enzymes.
Conjugating agent
 Conjugating bile acids
 Detoxification of benzoic acid → Hippuric
acid
As neurotransmitter
 Modulates NMDA
neurotransmission
 Moderate qty- inhibitor
 High levels- over-excitation
Metabolic errors
1. Primary hyperoxaluria -
Glyoxylate pathway affected-hereditary
defect in the enzyme Glycine transaminase-
Glyoxylate accumulates- ↑ urinary oxalate
irrespective of dietary intake
Protein targeting defect – enz seen in
mitochondria instead of peroxisome
Nephrolithiasis, renal colic, hematuria
2. Nonketotic Hyperglycinemia –
Defect in Glycine cleavage system
Severe mental retardation & seizures
WWW.VPACHARYA.COM
For more PPTs on Medical Biochemistry

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Glycine metabolism

  • 1. METABOLISM OF GLYCINE Prof (Dr)Viyatprajna Acharya MD, PhD (Biochemistry)
  • 2. OverviewofAAMetabolism  12 out of 20 AA- synthesised from intermediates of Glycolysis &TCA cycle  8 AA- essential AA; what are they? (I Love & Like To Take Potato Very Much)  Out of 12 NEAA- 9 from amphibolic intermediates  Rest 3 NEAA- Cys,Tyr, Hyl - from essential AA
  • 3. CatabolismofAA  Amino group- Urea  C-skeleton- 7 products Pyruvate Acetyl Co-A Acetoacetyl-CoA α-Ketoglutarate Succinyl Co-A Fumarate Oxaloacetate
  • 5. Ketogenic AA– AA that are degraded to Acetyl CoA or acetoacetylCo-A→ Ketone bodies Lysine & Leucine- Purely ketogenic
  • 6. GlucogenicAA AA that are degraded to Pyruvate, α- ketoglutarate, Succinyl CoA, Fumarate or Oxaloacetate Both Ketogenic & Glucogenic AA- Phe, Tyr, Trp & Ile
  • 7.
  • 9. GLYCINE  Simplest AA  Non-essential  Glucogenic
  • 10. Synthesis 1. From serine- removal of hydroxymethyl group from Ser 2. From Threonine- byThr aldolase activity 3. By Glycine synthase system- From CO2 , NH3 & 1-C unit; reversal of Gly cleavage system
  • 11.
  • 12. 4. Aminotransferase reaction- from Glyoxylate, Glutamate or alanine 5. From Choline Choline dehydrogenase Betaine dehydrogenase Methyltransferase Sarcosine demethylase Sarcosine oxidase
  • 13. Catabolism 1. Oxidative deamination by Glycine cleavage system- Multi-enzyme complex
  • 14. 1. Glycine dehydrogenase (decarboxylating) 2. Aminomethyltransferase GLYCINE CLEAVAGE SYSTEM OF LIVER MITOCHONDRIA
  • 15. 2. Glucogenic pathway- first gets converted to Ser- Reversal of serine hydroxymethyl transferase reaction Ser → Pyruvate
  • 16. 3.Biosynthesisoffollowing- Creatine, Creatine phosphate & Creatinine Heme Purine nucleotides Glutathione Conjugating agent Neurotransmitter
  • 17. Creatine & creatine phosphate (MAG)
  • 18.  During muscle contraction, energy is first derived from hydrolysis of ATP  Creatine kinase is present in – muscle, brain & liver  ATP regenerated by hydrolysis of creatine phosphate- LOHMANN’S REACTION  CK- where utilised?
  • 19.  Serum Creatinine level- 0.2-1.2 mg/dl  Creatine: • Dietary supplement • Used to improve athletic performance  Creatinine: • Urinary excretion generally constant;  proportional to muscle mass  Creatinine Clearance Test: • Compares the level of Creatinine in urine (24 hrs.) with the Creatinine level in the blood • Used to assess kidney function • Important determinant in dosing of several drugs in patients with impaired renal function
  • 22. 4. As a constituent of protein Plays a vital role in protein structure- present in turns & bends Every 3rd AA in collagen is Glycine
  • 23. GLUTATHIONE (GSH)  Tripeptide  Gamma-glutamyl-cysteinyl-glycine  Widely distributed in all tissues  GSH: GSSH (Reduced : oxidised) ratio is maintained at 100:1 by glutathione reductase
  • 24.
  • 25. Functionsofglutathione  Component of antioxidant enzyme glutathione peroxidase- scavenge free radicals  Maintains RBC membrane integrity. Protects Hb from getting oxidised by H2O2  Transport of AA- Meister cycle  Detoxification of drugs by increasing their solubility  Disulfide linkages in protein structure  Acts as a cofactor for some enzymes.
  • 26. Conjugating agent  Conjugating bile acids  Detoxification of benzoic acid → Hippuric acid
  • 27. As neurotransmitter  Modulates NMDA neurotransmission  Moderate qty- inhibitor  High levels- over-excitation
  • 28. Metabolic errors 1. Primary hyperoxaluria - Glyoxylate pathway affected-hereditary defect in the enzyme Glycine transaminase- Glyoxylate accumulates- ↑ urinary oxalate irrespective of dietary intake Protein targeting defect – enz seen in mitochondria instead of peroxisome Nephrolithiasis, renal colic, hematuria 2. Nonketotic Hyperglycinemia – Defect in Glycine cleavage system Severe mental retardation & seizures
  • 29.
  • 30. WWW.VPACHARYA.COM For more PPTs on Medical Biochemistry