Significance of Glycine

Glycine functions as an inhibitory neurotransmitter in the brain stem and the spinal cord. Its actions are antagonized by the rodenticide Strychnine, leading to twitching and muscle spasm.

The non availability of glycine can affect the synthesis of which of the following compounds?

A. Methionine

B. Hippuric acid

C. Glucuronic acid

D. Cysteine

E. Mercapturic acid.

Details

The correct answer is- B- Hippuric acid

Aromatic compounds like benzoic acid obtained from diet are detoxified by conjugation with glycine to form Hippuric acid (figure-1) which is excreted in urine.  This reaction takes place exclusively in liver. Hippuric acid excretion test is carried out to determine the functional status of liver. Sodium benzoate is given as a loading dose and the amount of Hippuric acid excreted in urine is estimated to determine the functional status of liver. The steps involved in the formation of Hippuric acid are summarized in figure-1. Many drugs, drug metabolites, and other compounds with carboxyl groups are excreted in the urine as glycine conjugates.

Synthesis of hippuric acid

Figure-1- Benzoic acid is initially converted to benzoyl CoA that conjugates with glycine to form Hippuric acid.

Although nutritionally glycine is a non-essential amino acid but functionally it is very essential. The important functions of Glycine can be summarized as follows:

i) As a constituent of protein

Glycine being a simple amino acid is found where the polypeptide bends as in beta bends or loops. A striking characteristic of collagen is the occurrence of glycine residues at every third position of the triple helical portion of the alpha chain. This is necessary because glycine is the only amino acid small enough to be accommodated in the limited space available down the central core of the triple helix.

ii) One carbon donor

The major pathway of glycine catabolism involves the cleavage of glycine to form CO2, NH4and NN10 Methylene tetra hydro folate (Figure-2). Hence it acts as a donor of one carbon fragment.

One carbon compound

Figure-2- The reaction is catalyzed by glycine cleavage system, N5, N10 Methylene tetra hydro folate acts as a carrier of one carbon fragment.

iii) Synthesis of Glutathione

Glutathione is a tripeptide containing three amino acids- Glutathione, cysteine and glycine (gamma glutamyl cysteinyl glycine). It is an important reducing agent, helps in maintaining the integrity of the red blood cells; also acts as a coenzyme in many reduction reactions.

iv) Synthesis of creatine

Creatine (methyl guanido acetic acid) is synthesized from three amino acids-Methionine, arginine and glycine. Methyl group is donated by Methionine; guanido group is contributed by Arginine and Acetic acid group comes from glycine. Creatine is stored in the muscle in the phosphorylated from- Creatine-P, a high energy compound.

v) Synthesis of purine nucleotide

Glycine contributes its entire structure for the formation of C4, C5 and N7 of purine nucleus (figure-3)

Purine structure
Figure-3- C4, C5 and N7 are derived from Glycine. Three amino acids – Glycine, aspartic acid and glutamine, contribute towards formation of purine ring.

vi)  Synthesis of bile salts

Cholyl co A derived from cholesterol conjugates with glycine to form Glycocholic acid, a bile acid which is secreted in the bile in the form of sodium salt- Sodium Glycocholate. Bile salts are required for the digestion and absorption of fats.

vii) Synthesis of heme

The two starting materials for heme synthesis are succinyl-CoA, derived from the citric acid cycle in mitochondria, and the amino acid glycine. By a series of reactions heme is synthesized that can be used for the synthesis of hemoglobin and other hemo proteins.

viii) Synthesis of Glucose

Glycine is glucogenic in nature. During the course of its metabolism it is converted to serine and that is non oxidatively deaminated to from pyruvate which can be further channeled towards pathway of gluconeogenesis.

ix) Glycine as a neurotransmitter

Glycine itself acts as neurotransmitter to regulate brain activities, as mentioned in the question.

As regards other options-

A. Methionine- Glycine is not a precursor for Methionine, which is an essential amino acid, it cannot be synthesized by the human body, and has to be provided in the diet.

C. Glucuronic acid- It is formed from glucose in the uronic acid pathway, glycine is nowhere required for its synthesis.

D. Cysteine- It is a non-essential amino acid and can be synthesized from Serine and Methionine. The carbon skeleton is acquired from serine whereas, the sulphur comes from methionine.

E. Mercapturic acid- It is a product of detoxification reaction, formed from conjugation of cysteine with xenobiotics.

 

 

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