Do Life style & change of food habits cause heart disease or is it a germ line mutation which causes cancer? It is a million dollar question to answer by scientists & clinicians. Atherosclerosis- In simple language, deposition of fats, proteins and debris leads to blockages in arterial system. It is generally thought that eating high fatty diet leads to deposition of fat into arteries. Does it meant that dietary fat is directly deposited into arteries ? That is why in recent days- Doctors/ dieticians prescribes low fatty diet with lots of fibres. It is a general concept that synthesis or more fat get deposited into arteries. This question is not answered yet by doctors or dieticians. But my concept was life style, food habit and exercise have no role to play in coronary artery disease. It is the change of mental status that stimulates signal transduction to trigger necessary course of actions and reactions and its ultimate results are expressed in diseased or healthy forms. For this reasons, I have selected few genes to find out the exact cause of heart ailment or other disease.

                First, I thought, it is the biosynthesis of lipids which must be depositing in arteries, hence I had selected a gene-Homo sapiens 1-acylglycerol-3-phosphate O-acyltransferase 1 (lysophosphatidic acid acyltransferase, alpha) (AGPAT1), transcript variant 1, mRNA- which catalyses conversion of lysophosphatidic acid to phosphatidic acid. In fact, both phospholipids are involved in signal transduction and lipid biosynthesis in cells. This gene is located on chromosome 6p21.3, an area within the class III region of the human major histocompatibility complex and this enzyme is present in endoplasmic reticulum.

                I found several patients with normal lipid levels, still having arterial blockages. Why? It means biosynthesis is normal, from where this deposits are coming on way? I thought it is the carrier molecules, those must be unable to carry the cargo, that is after synthesizing the molecules at subcellular level, it should be dispatched to particular destinations. Hence, I have selected the gene Homo sapiens coatomer protein complex, subunit zeta 1 (COPZ1), mRNA, which is present on chromosome 15, helps in intracellular protein, lipid transportation. The golgi complex functions at the cross roads of the secretary pathways, receiving newly synthesized proteins and lipids from endoplasmic reticulum, covalently modifying them, and then distributing the product to various final destinations. In addition, golgi recycles selected components back to endoplasmic reticulum. Golgi is organized as polarized stacks (Cis to Trans) of flattened cisternae enriched in transmembrane processing enzymes. Selective trafficking & retention of protein & lipid species within this system is mediated by cytosolic coat proteins that assemble onto golgi membrane, collect cargo and help impart curvature to the lipid bilayer so budding of forward/retrograde transport intermediates can occur.

              All biological processes are conducted through signal transduction. Signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemical reactions inside the cell, which are carried out by enzymes, activated by second messengers resulting in a signal transduction pathway. Such processes are usually rapid, lasting on the order of milliseconds in the case of ion flux, or minutes for the activation of protein- and lipid-mediated kinase cascades, but some can take hours, and even days (gene expression), to complete. In multicellular organisms, a multitude of different signal transduction processes are required for coordinating the behavior of individual cells to support the function of the organism as a whole. As may be expected, the more complex the organism, the more complex the repertoire of signal transduction processes the organism must possess. Thus, sensing of both the external and internal environments at the cellular level relies on signal transduction. Any error occuring during this process results in abnormal metabolic pathway leading to diseased condition. Many disease processes such as diabetes, heart disease, autoimmunity, and cancer arise from defects in signal transduction pathways.

             Cell-surface receptors are integral transmembrane proteins and recognize the vast majority of extracellular signaling molecules. Transmembrane receptors span the plasma membrane of the cell, with one part of the receptor on the outside of the cell (the extracellular domain), and the other on the inside of the cell (the intracellular domain). Signal transduction occurs as a result of stimulatory molecule or the binding of a ligand to its extracellular domain; the ligand itself does not pass through the plasma membrane prior to receptor-binding.

           Binding of a ligand to a cell-surface receptor stimulates a series of events inside the cell, with different types of receptor stimulation of different intracellular responses. Receptors typically respond to only the binding of a specific ligand. Upon binding, the ligand initiates the transmission of a signal across the plasma membrane by inducing a change in the shape or conformation of the intracellular part of the receptor. Often, such changes in conformation either result in the activation of an enzymatic activity contained within the receptor or expose a binding site for other signaling proteins within the cell. Once these proteins bind to the receptor, they themselves may become active and propagate the signal into the cytoplasm.

            Many of the enzymes activated as part of the signal transduction mechanism and also many adapter proteins have been found to possess specialized protein domains that bind to specific secondary messenger molecules. For example, calcium ions bind specifically to the EF hand domains of calmodulin, allowing this molecule to bind and activate Calmodulin-dependent kinase. PIP3, PIP2 and other phosphoinositides may bind to the Pleckstrin homology domains of proteins such as the kinase protein AKT again with activation activity.

                    Deactivation of effectors through intrinsic enzymatic activity. Either small or large G-proteins possess intrinsic GTPase activity, which controls the duration of the triggered signal. This activity may be increased through the action of other proteins such as GTPase-activating proteins (GAPS).

     The Notch protein sits like a trigger spanning the cell membrane, with part of it inside and part outside. Ligand proteins binding to the extracellular domain induce proteolytic cleavage and release of the intracellular domain, which enters the cell nucleus to alter gene expression.