ARGININE METABOLISM

2.  Arginine is highly basic, semi-essential amino
acid.
 Arginine is glucogenic amino acid.
 Arginine contains guanidinium group.
 Arginine is cleaved by arginase to liberate
urea & produce ornithine.

3.  Ornithine undergoes transamination of δ -
amino group to formglutamate γ –
semialdehyde which is converted to
glutamate.
 Hyperargininemia is an inborn error in
arginine metabolism due to a defect in the
enzyme arginase.

4.  Arginine is the substrate for the production
of nitric oxide (NO).
 The enzyme nitric oxide synthase (three
isoenzymes) cleaves the nitrogen from the
guanidino group of arginine to form NO.
 Requires NADPH, FMN, FAD, heme &
tetrahydrobiopterin.
 Very short half-life (about 5 seconds)

5. Arginine Citrulline
NO Synthase
O2 NO

6.  Neuronal NOS:
 NOS1 or nNOS or neuronal NOS is seen in
central & peripheral neurons.
 Nitrogenic neurons are seen especially in
cerebellum & gastrointestinal tract.
 It is mainly a cytoplasmic enzyme.
 It is activated by calcium.

7.  Macrophage NOS:
 NOS-2 or iNOS or inducible NOS or
macrophage NOS is mainly seen in
macrophages & neutrophils; but is also present
in hepatocytes.
 It is induced by cytokines (interleukin-1 &
tumor necrosis factor) & during inflammation.
 It is a cytoplasmic enzyme.
 Calcium does not activate this iso-enzyme.

8.  Endothelial NOS:
 NOS-3 or eNOS or endothelial NOS is seen in
endothelial cells, platelets, endocardium &
myocardium.
 In these sites, the NO is constantly produced
& released, so that arterial relaxation occurs.
 It is localized in the plasma membrane.
 It is activated by calcium.

9.  The role of nitric oxide as a therapeutic drug
(in the form of nitroglycerine and amyl
nitrate) for the treatment of angina.
 Nitric oxide acts as a mediator for several
biological functions.
 NO functions as a vasodilator & causes
relaxation of smooth muscles.

10.  It is a key molecule in the regulation of
blood flow & the blood pressure (inhibitors
of NO synthesis markedly raise blood
pressure).
 NO acts as an inhibitor of platelet
aggregation & adhesion.

11.  It functions as a messenger molecule of the
nervous system (neurotransmitter).
 NO mediates the bactericidal actions of
macrophages.
 It is involved in the erection of penis.

12.  NO promotes the synthesis of cGMP.
 Some of the actions of NO are mediated
through cGMP & protein kinase C.
 Agmatine:
 It is a derivative of arginine produced in the
brain.
 Agmatine possesses antihypertensive
properties.

13.  Angina Pectoris:
 Nitroprusside can directly release NO'.
(free radical)
 Nitroglycerine (glyceryl trinitrite) requires
glutathione to produce NO'.
 These will dilate coronary arteries & are
beneficial in treating angina pectoris.

14.  Pulmonary Hypertension:
 Inhalation of NO‘ is useful in the treatment
of pulmonary hypertension & high altitude
pulmonary edema.
 NO' produces pulmonary vasodilatation,
without lowering systemic blood pressure.

15.  Impotence:
 NO relaxes smooth muscles in the corpus
cavernosum & increases blood flow into the
penis & makes it erect.

16.  Textbook of Biochemistry – U Satyanarayana
 Textbook of Biochemistry – DM Vasudevan