7. ๏ Glycine can also be obtained from threonine,
catalysed by threonine aldolase.
Threonine Glycine + acetaldehyde
Threonine aldolase
7
8. ๏ Glycine can be synthesized by the glycine synthase
reaction from CO2, NH3 & one carbon unit.
๏ This is the reversal of the glycine cleavage system.
๏ It is a multienzyme complex.
๏ It needs the co-enzymes, NAD, lipoamide,
tetrahydrofolic acid & PLP.
8
From CO2, NH3 and One carbon unit
9. From CO2, NH3 and One carbon unit
CO2 + NH3 Glycine
Glycine synthase
complex, PLP
N5,N10 Methylene FH4 FH4
NAD+NADH + H+
9
12. Degradation of glycine
๏ Glycine undergoes oxidative deamination(reversal of
glycine synthase) to liberate NH4+, CO2 & one carbon
fragment as N5, N10 methylene THF.
๏ This provides a major route for glycine breakdown in
mammals.
12
18. Formation of purine ring:
๏ The entire molecule of glycine is utilized for the
formation of positions 4 & 5 of carbon & position 7 of
nitrogen of purines.
18
19. Synthesis of glutathione
๏ It is a tri-peptide containing glutamic acid, cysteine,
glycine.
๏ Present as reduced form (GSH) & oxidized form
(GSSG).
19
21. Synthesis of heme
๏ Glycine condenses with succinyl CoA to ฮด-amino
levulinate which serves as a precursor for heme
synthesis.
Glycine + Succinyl CoA Amino levulinate (ALA)
ALA Synthase
21
22. ๏ Creatine[ kreas(greek) : flesh]
๏ Present in the tissues as a high energy compound,
creatine phosphate
๏ Three amino acids glycine, arginine & methionine are
required for creatine formation.
22
23. ๏ 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 amido transferase to produce
guanidoacetate (glycocyamine).
23
25. Step-3:
๏ Creatine is reversibly
phosphorylated to
phosphocreatine (creatine
phosphate) by creatine
kinase.
๏ Lohmannโs reaction.
CREATINE KINASE.
25
26. Step-4:
๏ The creatine phosphate may be converted to its anhydride,
creatinine.
๏ It is a non-enzymatic spontaneous reaction.
๏ Creatinine is excreted in urine.
26
27. ๏ Normal serum creatinine level: 0.7 - 1.4 mg/dl.
๏ Serum creatine level: 0.2 - 0.4 mg/dl.
๏ Creatinine level in blood is a sensitive indicator of renal
function.
๏ In muscular dystrophies, blood creatine & urinary
creatinine are increased.
๏ The enzyme CK is elevated in MI.
27
28. ๏ Glycine is seen 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.
28
29. ๏ Glycine is seen where the polypeptide chain bends or
turns (beta bends or loops).
๏ In collagen, every 3rd amino acid is glycine.
29
30. Conjugation reactions
Conjugating agent, glycine performs two important
functions.
1. The bile acids - cholic acid & chenodeoxy cholic
acid- are conjugated with glycine.
Cholic acid + glycine Glycocholic acid
Chenodeoxy cholic acid + glycine Glycochenodeoxycholic acid
30
31. 2. Benzoic acid (preservative in foods).
๏ Glycine is used for detoxification of benzoic acid
to form hippuric acid.
Benzoyl CoA + glycine Hippuric acid + CoA
[Benzoyl glycine]
31
32. ๏ It is due to defect in glycine cleavage system.
๏ Glycine level is increased in blood, urine & CSF.
๏ Severe mental retardation & seizures are seen.
๏ There is no effective management.
32
33. ๏ This is a rare disorder.
๏ Serum glycine concentration is normal, but very high
amount (normal 0.5-1 g/day) is excreted in urine.
๏ It is due to defective renal reabsorption.
๏ It is characterized by increased tendency for formation of
oxalate renal stones.
๏ Urinary oxalate level is normal in these patients
33
34. ๏ It is due to protein targetting defect.
๏ Normally, the enzyme alanine glyoxalate amino
transferase is located in peroxisomes; but in these
patients the enzyme is present in mitochondria.
๏ So, enzyme is inactive.
๏ It characterized by increased urinary oxalate resulting in
oxalate stones.
34
35. ๏ Deposition of oxalate (oxalosis) in various tissues is
observed.
๏ The urinary oxalate is of endogenous origin & not due
to dietary consumption of oxalate.
๏ Primary hyperoxaluria is due to a defect in glycine
transaminase coupled with impairment in glyoxalate
oxidation to formate.
35
36. ๏ It is a milder condition causing only urolithiasis &
results from deficient activity of cytoplasmic glyoxalate
reductase.
๏ The management is to increase oxalate excretion by
increased water intake.
๏ Minimise dietary intake of oxalates by restricting the
intake of leafy vegetables, tea, beet-root etc.
36
38. 38
Histidine and beta alanine Carnosine (Antioxidant )
Beta alanine and N-
methylhistidine
Anserine (Antioxidant )
Ornithine Polyamine
39. Gamma Amino Butyric Acid (GABA)
39
๏ Glutamic acid is decarboxylated to GABA.
40. 40
๏ GABA is an inhibitory neurotransmitter
๏ It opens the chloride channels in post-synaptic membranes
in CNS.
๏ Both the formation and catabolism of GABA requires pyridoxal
phosphate as co-enzyme Therefore, in pyridoxine deficiency the
metabolism of glutamate by the GABA shunt pathway is affected.
41. 41
๏ Since GABA is an inhibitory transmitter, a low level
of GABA or deficiency of pyridoxal phosphate would
lead to convulsions.
๏ Sodium valproate which inhibits GABA oxidase
is used in the treatment of epilepsy.
42. Synthesis of Nitric Oxide
42
๏ Nitric oxide is formed from arginine by the enzyme nitric
oxide synthase (NOS). It contains heme, FAD, FMN
and tetrahydrobiopterine.
๏ The enzyme utilizes NADPH and molecular oxygen.
Calmodulin is required to modulate its activity.
๏ The guanidino nitrogen of arginine is incorporated into NOห.
๏ From the molecular oxygen, one atom is added to NOห and
the other into citrulline.
๏ Therefore, the enzyme is a di-oxygenase .
44. Histidine to histamine
44
๏ Histamine is formed from histidine by
decarboxylation,catalyzed by histidine
decarboxylase.
45. Summary of action of histamine
45Tissue Effect
1. Blood vessels Pulmonary venous dilation;
Superficial
temporal artery dilation
(migraine).
Large
veins, smaller venules and
capillaries are
dialated
2. Cardiovascular
system
Fall in BP; increased capillary
permeability
3. Heart coronary artery flow is increased
4. Smooth
muscles
Direct stimulant; contraction of
bronchial
muscles; bronchospasm
5. Exocrine glands Stimulates gastric acid secretion
46. References
1. TEXTBOOK OF BIOCHEMISTRY FOR MEDICAL STUDENTS,
7TH Ed., DM VASUDEVAN, SREEKUMARI
2. BIOCHEMISTRY, U.SATYANARAYANA, U.CHAKRAPANI, 4TH
Ed.
3. LEHNINGER PRINCIPLES OF BIOCHEMISTRY,DAVID L.
NELSON, MICHAEL M. COX, 5TH Ed.
4. TEXTBOOK OF BIOCHEMISTRY, THOMAS M. DEVLIN, 6th Ed.
46
