Protein Ligand Essay

Most Americans have heard of Ritalin and Adderall, either being used to calm hyperactive children or used illegally across every college campus for the purpose of studying. These are two completely different circumstances, which may be confusing to some. The reason that these two different groups of people get two vastly different results from the same drug is that these belong to the drug class of central nervous system (CNS) stimulants. CNS stimulants increase alertness mentally and physically, but do the opposite for those with hyperactivity disorders. This is because these drugs release dopamine levels in the brain. Dopamine is a chemical in the brain that is related with motivation (Healthline Editorial Team).

Of the six most common neurotransmitters, dopamine is probably the one people know the most about. Dopamine is involved in controlling the reward and pleasure system in the brain. It allows us to recognize rewards and helps give us the ability to go after them. Learning, behavior, and cognition are also affected by dopamine levels. As with anything, if you have an imbalance, then bad things can happen. Parkinson’s disease can be caused by low dopamine amounts. People who have low dopamine levels can be addicted to substances easier.

Because of the prevalence of copious quantities of dopamine in people who have schizophrenia, most medications attempt to prevent the buildup of dopamine by blocking it in the striatum. Other methods in which drugs for this condition help to counteract the effects of dopamine, however, are more indirect. There are medications that are under development that "interfere with glutamate signals in the brain" (Nauert, 2010) that are targeted towards affecting glutamate, which in turn will then positively influence the levels of dopamine that the brain releases. In both ways then, (direct and indirect), dopamine is the primary focus of schizophrenia medication.

In humans/animals, the main cells that store fat for energy are adipocytes. These fat cells are found under the skin, in the abdominal cavity and surround major organs. The fatty tissue is the body’s main means of storing energy for long periods of time. Lipids, like triglycerides are stored in the adipocytes until ready to be used by the body for energy. Fat is broken down through metabolism in the mitochondria of the cell. The triglycerides are broken down into glycerol and 3 fatty acids. The glycerol can be easily converted to glyceraldehyde 3 phosphate, an intermediate of glycolysis. From there it can go through the Krebs Cycle and electron transport chain to make ATP. The 3 fatty acids can be broken

Information from the nigra cells passes through the synapses with the aid of a specific hormone, dopamine, which is a significant chemical transmitter in the brain. Because the existence of dopamine is essential to the function of the substania nigra, it is also essential for the various muscular activities controlled by the striatum, such as walking, balance, etc. (16).

Cell-surface receptors are integral membrane proteins that play a major role in signal transduction, allowing the function of Neurons, muscles and sensory organs to occur. Their basic function is to carry out the process of signal transduction by binding to an extracellular signalling molecule. Cell-surface receptors regulate gene transcription, ion flux in the neurons and growth factors. This regulation allows the human body to function with little error. They detect the smallest of changes and respond with a cascade of signalling events appropriately. I am going to describe the four main types of cell-surface receptors and the Mitogen-activated protein cascade in receptor tyrosine kinases.

Every day, your brain maintains a delicate balance between chemicals that push its cells to fire and opposing chemicals that pull its cells back toward inactivity. Two of the most common neurochemicals that play this tug of war are glutamate and GABA, both of which are classified as neurotransmitters, chemical messengers that communicate between neighboring brain cells. The purpose of glutamate is to elicit action, while the function of the GABA neurotransmitter is to restore calm.

There is substantial evidence showing possible neurotransmitter dysfunctions or imbalances in children with ADHD, especially in dopamine pathways, which play a major role in reward-motivated behavior and are involved in motor control behaviors (Volkow et al., 2011). Children diagnosed with ADHD have demonstrated lower levels of dopamine in the brain in comparison to typical children, a difference that could explain their lack of impulse control. For that reason, psychotropic medication such as Ritalin have become the treatment of choice of many doctors and parents alike in order to regulate the dopamine levels in the neurocognitive system of ADHD children. These children tend to respond well to stimulants because they act by changing the availability of dopamine in the brain during synapse, that is, it block the reuptake of dopamine by the neuron from which it was released, and increase the amount of dopamine circulation in the brain. These effects of dopamine may

Different GRK subtypes combined with the action of -arrestins can contribute the endocytosis of Group I mGluRs in an agonist-dependent manner; however, the results are inconsistent (reviewed in Refs: Iacovelli 2013, Kim 2008). Both GRK2 and GRK4 induce the agonist-induced internalization of mGluR1a, which appears to require GRK2-mediated phosphorylation of the S869-V893 region of mGluR1a when expressed in HEK cells (Iacovelli 2003, Sallese 2000, Mundell 2003). These agonist-induced internalization processes are -arrestin 1/2 and dynamin-dependent (Mundell 2001, 2002, 2003). -arrestin 1 appears to be important in mGluR1 endocytosis; however, the agonist-stimulated internalization of mGluR1a is observed only when -arrestin 1 is co-expressed with either GRK2 or GRK5 in HEK cells. GRK2, GRK5, -arrestin 1, or -arrestin2 individually has no significant effect on the internalization of mGluR1a (Dale 2001). -arrestin 1, but not -arrestin 2, selectively interacts with mGluR1a and is redistributed to the same

In the year 2002, the US reached a land mark decision when the Sarbanes Oxley act was finally affected into law which principally changed the way auditing and financial reporting was being conducted. This act was prompted by high level frauds that public companies engaged in with regard to financial reporting and auditing practices. The act therefore recommended the setting up of a Public accounting Oversight board which was mainly to conduct regulatory and supervisory roles in auditing public audit firms and individual auditors. This was done through establishment of proper quality control measures on the work of auditors to minimize the audit risks that firms could face while conducting their work. The Ligand Pharmaceuticals case

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors (1), participate in lipid and glucose metabolism (2,3) respond to a wide variety endogenous and exogenous ligands (4). There is three subtypes, PPAR훼, PPAR훽/훿, and PPAR훾 , are known (2). PPAR훼 is expressed in heart, intestine, skeletal muscle, adipose tissue and kidney. PPAR훽/훿 is presented in all tissue. PPAR훾 is mainly presented large intestine, heart and adipose tissue (5,6) . PPAR훼 is highly presented in cardiomyocyte more than PPAR훾 (60).

The physiological function of each receptor subtype has not been established and is currently the subject of intensive investigation (1).

There are two generally kinases which are G protein coupled receptor kinase GRKs and second messenger-dependent protein kinases(e.g., PKA and PKC). The G protein coupled receptor kinase only act on the phosphorylate agonist activate receptor. For example, GRK family members work on activated receptors, and then promote the binding of cytosolic arrestins, which sterically uncouple the receptor from heterotrimeric G protein. In contrast, second messenger-dependent proteins kinases act on both phosphorylate agonist-activated GPCRs and other phosphorylates receptors that have not been exposed to agonist. Thus, agonist-independent phosphorylation can only happen with the second messenger-dependent protein kinases, but GRKs cannot do it. When we recognize the

Norepinephrine is the most predominant transmitter in the body and its receptors are found in the locus ceruleus, projecting throughout the rest of the brain. The transporters responsible for reuptake of norepinephrine depends on the presence of extracellular sodium and calcium to function. Norepinephrine is primarily responsible for the stress response and also awareness of surroundings, attention, learning, memory, sleep and arousal. Dopamine is primarily found in the brain and there are numerous receptors and pathways that dopamine uses to influence learning, clarity of memories, judgment/insight, pleasure, motivation, and complex motor movements. Because of its effects, dopamine is often targeted in addictive behaviors, psychosis, Parkinson’s

Catalytic receptors are characteristically dimeric cell surface proteins that contain a single transmembrane domain which separates an extracellular ligand binding site and an intracellular enzymatic activity. Receptors with extrinsic tyrosine kinase activity and intrinsic protein serine/threonine kinase activity form minor subfamilies in this group2.