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.

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.

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)

Arginine CitrullineNO Synthase

O2 NO

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.

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.

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.

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.

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.

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.

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.

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.

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.

Impotence:

NO relaxes smooth muscles in the corpus

cavernosum & increases blood flow into the

penis & makes it erect.

Textbook of Biochemistry – U Satyanarayana

Textbook of Biochemistry – DM Vasudevan