glucine

2. Content
1) Chemistry
2) Overview of glycine metabolism
3) Synthesis of glycine
4) Degradation of glycine
5) Specialized products from glycine
6) Disorders

3.  Simple amino acid
 Non essential amino acid
 Metabolically - glucogenic amino acid
 Involved in one-carbon metabolism
 Present in the interior structure of protein, eg:
Collagen,every 3rd aa is glycine
 Specialized products synthesized form glycine,eg:
heme, purines, creatine etc.

5. Glycine is synthesized :
 From Serine
 From Threonine
 From CO2, NH3
 From Glyoxalate

6.  Glycine is synthesized from serine by the enzyme serine
hydroxymethyl transferase which is dependent on
tetrahydrofolic acid (THFA).
 Beta carbon of serine is removed : enters one carbon pool
with help of THFA
 Alpha cabron of serine : becomes alpha carbon of glycine

8. Synthesis of deoxythymine
nucleotides

9. From serine
Serine Glycine
Serine hydroxy methyl
transferase
N5,N10 methylene
THFA
THFA

10.  Glycine can also be obtained from threonine,
catalysed by threonine aldolase
Threonine Glycine + acetaldehyde
Threonine aldolase

12. From CO2, NH3
 Glycine can be synthesized by the glycine synthase
reaction from CO2, NH3 & one carbon unit
 Reversal of the glycine cleavage system
 Multienzyme complex
 Needs co-enzymes NAD, lipoamide, THFA & PLP

13. From CO2, NH3
CO2 + NH3 Glycine
Glycine synthase
complex, PLP
N5,N10 Methylene
THFA THFA
NAD+
NADH + H+

14.  Glycine amino transferase:
catalyze the synthesis of glycine from glyoxylate &
glutamate or alanine
 This reaction strongly favors synthesis of glycine

15. Glyoxalate Glycine
alanine pyruvate
Glycine amino-transferase /
alanine glyoxalate amino
transferase
PLP

17. Degradation of glycine
 Glycine : oxidative deaminaion (by reversal of glycine synthase) :
to liberate NH3, CO2 & one carbon unit as methylene THFA
 It is a multienzyme complex
 It requires co-enzymes -NAD, Lipoamide, THFA, PLP
 PLP-dependent glycine decarboxylase
 Lipoamide containing amino methyltransferase
 Methylene THFA synthesizing enzyme
 NAD+ dependent lipoamide dehydrogenase
 Major route for glycine breakdown in mammals

19.  Glycine converted to serine,reversal of serine
hydroxy methyltransferase reaction
 The serine is then converted to pyruvate by serine
dehydratase
 Pyruvate serves as a precursor for glucose

21. Synthesis of specialized products from
glycine
1) Creatine,creatine phosphate & creatinine
2) Heme
3) Purine nucleotides
4) Glutathione
5) Conjugating agent
6) Neurotransmitter

22.  Creatine: present in the muscle tissues as a high energy
compound, phosphocreatine & as free creatine
 Three amino acids glycine, arginine & methionine:
required for creatine formation

24. Step-1:
 The first reaction occurs in the mitochondria of
kidney & pancreas
 It involves the transfer of guanidino group of arginine
to glycine, catalysed by glycine- arginine
amidotransferase to produce guanidoacetate

25. Step-2:
 S-Adenosylmethionine (active methionine)
donates methyl group to guanidoacetate to
produce creatine
 This methylation reaction occurs in liver

26. Step-3:
 Creatine : reversibly phosphorylated to
phosphocreatine (creatine phosphate) by creatine
kinase, needs hydrolysis of ATP
 phosphocreatine : stored in muscle as high energy
phosphate, serves as an immediate store of energy in
the muscle

27. During muscle contraction, energy from
hydrolysis of ATP
ATP regenerated by hydrolysis of creatine
phosphate, c/a Lohmann’s reaction

29. Step-4:
The creatine phosphate: converted to
creatinine
Non-enzymatic spontaneous reaction
Creatinine : excreted in urine

31.  Normal ranges of creatinine & creatine:
 Serum level:
Serum creatinine : 0.7 - 1.4 mg/dl
Serum creatine : 0.2 - 0.4 mg/dl
 Urine level:
 Creatinine: 1 - 2 gm/day
 Creatine: 0 - 50 mg/day

32.  Creatinine level in blood sensitive indicator of renal
function, Creatinine Clearance – measure of GFR
 In muscular dystrophies, blood creatine,creatinine &
urinary creatinine are increased
 Elevated serum creatinine: in renal failure,fever,starvation
 The enzyme CK is elevated in Myocardial infarction

33.  Excretion of creatinine: constant for an individual
depends on muscle mass
 Normally , urine contains – creatine (less)
 Creatinuria – increased excretion of creatine in
urine : in Muscular dystrophy

34. Synthesis of heme
 Glycine condenses with succinyl CoA to form δ-
amino levulinic acid
 which serves as a precursor for heme synthesis
Glycine + Succinyl CoA Amino levulinate (ALA)
↓
Precursor for Heme Synthesis
ALA Synthase

35.  The entire molecule of glycine is utilized for the
formation of positions 4 & 5 of carbon & position 7 of
nitrogen of purines ( C4,C5 & N7)
Synthesis of purine ring

36. Synthesis of glutathione
 Tri-peptide, containing glutamic acid, cysteine,
glycine
 Reduced form (GSH) & Oxidized form (GSSG)
 Important in maintaining RBC membrane integrity

38. Conjugation reactions
 Conjugating agent, glycine performs two important
functions
 The bile acids:
 Cholic acid & chenodeoxy cholic acid- are conjugated
with glycine
Cholic acid + glycine Glycocholic acid
Chenodeoxy cholic acid + glycine Glycochenodeoxycholic acid

39.  Benzoic acid : used as preservative in food
 Benzoic acid is used to detoxify amino nitrogen in
the form of glycine = forms benzoyl glycine, water
soluble compound, easily excreted
Benzoyl CoA + glycine Hippuric acid/benzoyl
glycine +
CoA

40.  Glycine : in the brainstem & spinal cord
 Glycine opens chloride specific channels
 In moderate levels,
Glycine inhibits neuronal traffic;
but at high levels, it causes over-excitation

41.  Glycine: seen where the polypeptide chain bends or
turns (beta bends or loops)
 In collagen, every 3rd amino acid is glycine

42.  Non-ketotic Hyperglycinemia (NKH):
Due to defect in glycine cleavage system
Glycine level: increased in blood, urine & CSF
C/F: Severe mental retardation & seizures
No effective management

43.  Rare disorder
 Serum glycine concentration normal/decreased,
but very high amount (normal 0.5-1 g/day) excreted in
urine
 Due to defective renal reabsorption
 characterized by increased tendency for formation of
oxalate renal stones

44.  Due to protein targetting defect (AR)
 Normally, the enzyme alanine glyoxalate amino
transferase is located in peroxisomes;
but in these patients the enzyme is present in
mitochondria/cytoplasm
 So, enzyme is inactive
 Results in excess production of oxalates, comes in urine

46.  Renal deposition of oxalates: nephrolithiasis,renal
colic, hematuria
 Extrarenal oxalosis: seen in heart, blood vessels &
bone

47.  Milder condition causing only urolithiasis
 Results from deficient activity of cytoplasmic
glyoxalate reductase/oxidase

48. Management :
To increase oxalate excretion by increased
water intake
Minimise dietary intake of oxalates by
restricting the intake of leafy vegetables, tea,
beet-root etc.

50. Thank You