synthesis and degradation of glycine is discussed. specialized products formed from glycine is described in detail. disorders associated with metabolism of glycine is also explained.
1. Dr . N. Sivaranjani
Asst Prof
Metabolism of Glycine
2. CHEMISTRY OF GLYCINE :
CH
COOH
NH2
H
• Glucogenic A.AMetabolic
fate
Nutritional
Optically
inactive
Simplest
AA
• Non-Essential A.A
• Absence of Asymmetric C
• R group -H
Dr. N. Sivaranjani
6. Reversal of glycine cleavage system
Glycine Synthase
Glycine
COOH
NH2
H
CH
N5N10
MethyleneTHFTHFA
CO2 + NH3
NADH + H+
NAD
lipoamide Reduced lipoamide
Dr. N. Sivaranjani
12. Glucogenic pathway
COOH
NH2
H
CH
Glycine
Serine hydroxy methyl
transferase
PLP
THFA
N5,N10
Methylene
THFA
Serine
COOH
NH2
CH2OH
CH
C
COOH
O
CH3
Pyruvate
NH3
H2O
Serine
dehydratases
Glucose
GLUCONEOGENESIS
Dr. N. Sivaranjani
13. Glyoxalate – Oxidative Deamination
Glycine Oxidase
Formate
Glycine FADH2FAD Glyoxalate
Oxalate
NH3 One
carbon
O2H2O2
H2O + ½ O2
Catalase
CO2
½ O2
COOH
NH2
H
CH
COOH
H
C O
H-COOH
COOH
COOH
Excreted
Dr. N. Sivaranjani
15. Collagen synthesis
Small , non-polar - Glycine is present
in interior bends / turns
Collagen (30%) – every 3rd A.A – Glycine (X-Y-Gly)n
Most abundant a.a - excreted in urine
Protein synthesis
Dr. N. Sivaranjani
16. Heme –
Key enzyme
ALA
synthase
PLP
δ -Aminolevulinic
acid (ALA)
+
CO2
Heme
Succinyl CoA
Glycine
COOH
NH2
H
CH
COOH
CH2
CH2
C O
S—CoA
CH2
CH2
C O
CH2—NH2
COOH
CoA-SH
Dr. N. Sivaranjani
17. CREATINE & CREATININE
Glycine
COOH
NH2
H
CH
COOH
NH
CH-NH2
C NH2
NH2
(CH2)3
Arginine
+
COOH
NH2
CH-NH2
(CH2)3
COOH
NH
C NH2
NH2
CH2
+
Ornithine Guanido
acetic
acid
Glycine Arginine amido
transferaseMitochondria
Kidney and pancreas
Dr. N. Sivaranjani
23. Blood Level :
Creatinine - 0.7 to 1.4 mg/dl
Creatine – 0.2 to 0.6 mg /dl
Urine level :
Creatinine – 1 to 2 gm /day
Creatinine excretion for each individual is constant
Creatine – 0 – 50 mg / day – normally very less
Creatine & Creatinine
Dr. N. Sivaranjani
24. Serum Creatinine– sensitive indicator of renal function
Excretion of Creatinine is constant for an individual
which depends on muscle mass.
Creatinine Clearance – measure of GFR.
Normally , urine contains – creatine (less)
Creatinuria - ↑ Creatine in urine
Muscular dystrophy
Hypogonadism
Hyperthyroidism
D.M
Stravation
Creatine Kinase – Cardiac Marker.
Dr. N. Sivaranjani
25. Tripeptide – Glutamic acid , Cysteine
, Glycine.
example for Pseudopeptide
Present as - Reduced form (GSH)
Oxidized form (GSSG).
Ratio of GSH:GSSH = 100:1 – Mandatory for
optimum activity
Glutathione
Dr. N. Sivaranjani
28. G
L
U
T
A
T
H
I
O
N
E
Transport of Neutral AA in intestine &
kidney – MEISTER CYCLE
Scavenges Free
radical
Maintains RBC integrity
Converts
Met Hb to
Hb
Detoxification
Coenzyme
for some
reaction
Keeps enzymes in active state
Dr. N. Sivaranjani
29. – C4, C5 , N7 of purine ring
Purine bases
C
N
N
N
C
C
C
C
N 1
2
3
4
5
6
7
8
9
CH2
COOH
NH2
Glycine
Dr. N. Sivaranjani
30. Peroxisomes
Cholic acid / +
Cheno-deoxycholic acid
Glycocholate / Glycochenodeoxycholate
Conjugation – lowers Pka of Bile Salts
↑ efficiency of bile acids as SURFACTANTS
Conjugation of Bile acids
Glycine
Dr. N. Sivaranjani
31. Solubilize Cholesterol in bile
Excretion of Cholesterol
Bile Salts – Sodium / Potassium salts of primary
Bile acids
Emulsification ,absorption of TAG , Fat Soluble
Vitamin
Functions
Dr. N. Sivaranjani
32. Detoxification of Benzoic acid
- Occurs in Liver – Index of liver function
- Benzoic acid – Food Preservative.
Benzoic acid + Glycine
Benzoyl Glycine / Hippuric acid
Treatment in Urea cycle disorders
Dr. N. Sivaranjani
33. As an inhibitory neurotransmitter - brainstem ,
spinal cord.
Opens chloride specific channels
Moderate levels glycine - inhibits neuronal
traffic
High levels - over-excitation.
Neurotransmitter
Dr. N. Sivaranjani
34. Inborn Errors of glycine metabolism –
Disorders
Non-Ketotic Hyperglycinemia
Glycinuria
Primary Hyperoxaluria
Dr. N. Sivaranjani
35. Defect – Glycine Cleavage System
Autosomal Recessive
Mental Retardation , Seizures in children
↑ Glycine in blood ,CSF , Urine
NO effective treatment
Non-ketotic Hyperglycinemia
Dr. N. Sivaranjani
36. Rare, Autosomal Recessive .
Defect – Renal tubular reabsorption of Glycine,
Proline
↑ Excretion of Glycine , Proline in urine but
Serum Glycine – Normal
↑ risk of Oxalate stones but urinary Oxalate –
normal.
Glycinuria
Dr. N. Sivaranjani
37. Rare , Autosomal recessive
Normal excretion - 50 mg/day
Defect –Glycine transaminase
impaired oxidation of Glyoxalate to formate
Defect in protein targeting –
so , Transaminase is in mitochondria instead
of peroxisomes.
Primary Hyperoxaluria
Dr. N. Sivaranjani
38. Formation of oxalate
Glycine Oxidase
Formate
Glycine
FADH2FAD
Glyoxalate
Oxalate
NH3
X
X
• Failure to catabolize Glyoxylic acid
normally
• Subsequent oxidation of Glyoxylic acid
to Oxalate
Glycine transaminase
Dr. N. Sivaranjani
39. ↑ Urinary Oxalate (upto 600mg/d,normal-50mg/d)
oxalate crystals deposited in various tissues-
Oxalate renal stones – calcium oxalate
Renal colic, Urolithiasis, Nephrocalcinosis,
hematuria, renal failure.
Oxalate deposition - Extra Renal tissue
Extrarenal Oxalosis - Heart, blood vessels,
bone.
Dr. N. Sivaranjani
40. Treatment :
↑ water intake – increases oxalate excretion
↓ oxalate in diet – spinach , beet-root ,
tea, sesame seeds.
Dr. N. Sivaranjani
