On the use of GMOs (a) The biosynthesis of amino acids in plants occurs in the l

Question

On the use of GMOs (a) The biosynthesis of amino acids in plants occurs in the leaves, but amino acids are needed in the tubers of potatoes. How do amino acids get from the leaves to the tubers? (b) McDonalds is very interested in GMO potatoes- why? (c) How can reduction of asparagine synthetase in leaves change the amount of acrylamide in french fries and potato chips? How have companies reduced asparagine synthetase? (d) Faulty asparagine synthetase activity in humans has been linked to acute lymphoblastic leukemia. Rather than gene knockouts as in potatoes, small molecule inhibitors might prove more effective. What is the structure of human asparagine synthetase? Based on its structure, discuss your approach to designing an inhibitor of this enzyme. Justify your reason

Explanation / Answer

(a) Efficient biosynthesis of amino acid and its translocation throughout the plant tissues plays a vital role in plant growth. Recent studies have identified the genes regulating the export of the synthesised amino acids post uptake of nitrogen by the roots. Putative transporter and regulator proteins are also suggested to function in the partitioning of amino acids. While another plausible mechanism involves the phloem (living vascular tissue) which gets enriched in soluble organic nitrogen compounds and thereby transfers them to various organs of the plant.

(b) A gmo potato is one which has been genetically modified to incorporate the advantages of being pest resistant, absence of browning etc. Mc Donalds has infact resisted to the use of GMO potatoes inspite of its largest potato supplier coming up with the GMO variety of potato. Anti GMO opinions mostly point out the fact that the cultivation of GMO crops would in turn lead to the use of higher amounts of pesticides since GMO foods would exhibit high pest resistance and thereby lead to pesticide and antibiotic resistance in insects and bacteria thus causing a global alarm. Also quality and thereby brand name are important factors which have made Mc Donalds resist the use of GMO potatoes.

(c) The most widely available amino acid in potatoes is aspargine. Aspargine synthetase is the chief enzyme involve in the synthesis of aspargine from aspartate by amidation. Aspargine in turn is the precursor for carcinogenic acrylamide, by reacting with reducing sugars present in starchy food at cooking temperatures. Thus reducing the aspargine synthetase in turn reduces the proportion of acrylamide in processed preparations like french fries and chips.

The modern method of reducing the aspargine synthetase involves silencing the genes playing role in the ATP dependent biosynthesis of aspargine and thereby reducing its accumulation.

(d) Human aspartate synthetase enzyme possibly contains two domains-N-terminal catalyzes the transformation of glutamine into glutamic acid along with ammonia. While the C-terminal facilitates the reaction of aspartate with ATP to yield reactive intermediates.

Approaches for the design of small molecule enzyme inhibitors involve of the understanding of the enzyme structure followed by the identification of the enzyme's active site residues. One also needs to consider the detailed reaction mechanism through which the enzyme operates. This involves the reaction intermediates, transition states and reaction kinetics. Identification of the active site provides the route of inhibition via mutation of the key residues involves in the catalytic activity of the enzyme. While interefernce of small molecule inhibitors with the intermidates or transition states reduces the overall enzymatic activity. Thus one needs to consider both the factors along with inhibition activity at very low concentration for designing of inhibitor of aspartate synthetase enzyme.

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