The tryptophan (trp) operon system is a type of repressible operon system. It was worked out by Jacob and Monod in 1953.

The 20 amino acids are required in large amounts for protein synthesis and E.coli can synthesize all of them. The genes for the enzymes needed to synthesize tryptophan are generally clustered in trp operon and are expressed whenever existing supplies are limiting.

When tryptophan is present, it binds the trp repressor and induces a conformational change in that protein, enabling it to bind the trp operator and prevent transcription (operon is repressed).

The E.coli trp operon includes five trp genes (trp E, D, C, B, A) that encode enzymes required to convert chorismate to tryptophan.

The gene products are:

trpE – anthranilate synthetase

trpD – phosphoribosyl anthranilate transferase

trpC – phosphoribosyl anthranilate isomerase-indole glycerol phosphate synthetase

trpB – tryptophan synthetase β

trpA – tryptophan synthetase α

Mechanisms:

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Definition

Restrictive lung diseases are usually chronic, diffused, lung interstitial diseases, usually effecting the most peripheral and delicate interstitium of the alveolar walls.

What is pulmonary Interstitium?

Pulmonary interstitium is composed of basement membranes of the alveolar epithelial cells, vascular endothelial cells, and the tissue between them, mostly made of elastic fibers, collagen, fibroblasts that make more elastic fibers, smooth muscle cells, mast cells, and sometimes mononuclear cells.

In the peripheral parts of the lung where the alveoli are numerous the interstitium is thin and delicate. Sometimes composed of only the two basement membranes fused together.

Respiratory membrane

Figure: Components of the interstitium. Note the alveolar macrophage is not a part of this interstitium. Also, in peripheral areas the interstitium is minimal causing the two basement membranes to fuse.

Hallmark of the restrictive lung diseases

Reduced compliance of the lungs. That is, the lungs are so stiff that they cannot expand easily. Patient has to exert more energy to pull air in the lungs. This is dyspnea.

Damage to the alveolar epithelium and pulmonary vessels hinders gas exchange leading to hypoxia.

Causes of the restrictive lung diseases

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The Human Genome Project

Francis Collins

The genome is the ultimate source of information about an organism. Advances in genetic engineering techniques made it possible for the scientists to isolate and clone DNA pieces and determine nucleotide sequences of these genome. After the development of practical DNA sequencing methods, serious discussions began about the prospects for sequencing the entire 3 billion base pairs of the human genome. The international Human Genome Project got underway with extensive funding in the late 1980s. The effort eventually included significant contributions from 20 sequencing centers distributed among six nations: the United States, Great Britain, Japan, France, China, and Germany. General coordination was provided by the Office of Genome Research at the National Institutes of Health, led first by James Watson and after 1992 by Francis Collins.

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