Calpain was first discovered within the brain, lens of eyes and other tissues by Gordon Guroff in 1964. This was done by isolating enzymes in both rat brains and skeletal muscles. These findings concluded that Calpains are calcium-dependent cytosolic cysteine proteinases. With further research, it was noted that Calpains are found in nearly all eukaryotes as well as some types of bacteria but, not within archaebacterial domain. Structurally, Calpains contain four functional domains with two domains that serve as regulatory subunits. In general, Calpains have multiple functions such as cell cycle progression, cell differentiation, membrane fusion, signal transduction, membrane fusion, apoptosis and myogenesis (Khorchid & Mitsuhiko, 2002). …show more content…
Only a few classical Calpains have been identified within invertebrates. Specifically for human Calpain genes, there are nine classical Calpains and six non-classical Calpains, giving a total of 15 Calpain genes for humans. For human Calpain genes, there two genes for regulatory subunits and one specific inhibitor protein. Classical Calpains, especially those found in humans, are ubiquioltly expressed and are controlled through the inhibitor of Calpastain (Trinchese et al., 2008). Although the role of calcium inducing change to enable Calpastatin to bind to Calpain is unknown, it is seen that Calpain 2 is bounded by inhibitory domains of Calpastatin which are inhibiting Calpain from both sides of the active site cleft. From this it was assumed that Calpastatin not only recognizes that there are multiple lower affinity sites but, that they are only present in the calcium-bound form of the enzyme which results in the interaction between Calpain and Calpastatin to be tight, specific and calcium dependent (Hanna, Campbell, & Davies, 2008). Aside from Calpains causing cells to migrate, differentiate, proliferate and die, activation of Calpains have been linked to the pathogenesis of Alzheimer’s Disease. 5 million individuals have been diagnosed with Alzheimer’s Disease with an increase of 68 percent from 2000-2010, making it the sixth leading cause of death within
Alzheimer’s Disease is a disease of the future. With the growing aged population, this disease, which affects primarily the elderly, will become of increasing relevance to the medical profession. Also, the high frequency of Alzheimer’s, and the high cost in labor, money, and material of caring for its victims shall put considerable burden on the society as a whole. Here, however, these issues are not going to be debated. Instead the pathology of Alzheimer’s will be reviewed to the extent it is known today.
Creatine phosphate has been heavily experimented upon to show that it is an important effector towards muscle activity. When creatine phosphate is present in a solution containing muscle fibers without the presence of ATP, it serves as the energy supplier due to the fact that it absorbs bound adenine nucleotide, which is firmly linked to the contractile elements on muscle fibers (Bozler, 1953). Even in low concentrations this nucleotide can be considered an energy transfer mechanism, for it takes full advantage of the creatine phosphates energy supply, thus acting as a substrate for the enzymatic activity of the contractile elements of a muscle group. Consumption of this nucleotide leads to an increase in the strength of contraction. Creatine phosphate also speeds up rate of relaxation of muscles, for it induces the relaxing effect of ATP (Bozler, 1953). Thus, this research suggests that creatine phosphate is directly linked to instigate muscle contractibility.
EDMAN KA & SCHILD HO 1962, ‘The need for calcium in the contractile response induced by acetylcholine
Tenapanor acts on the twelve transmembrane protein channel known as the sodium hydrogen exchanger 3 (NHE3) which work how the name would suggest. By binding to this channel tenapanor blocks the sodium from being absorbed at the intestinal level which leads to it traveling straight through the body instead of being filtered by the kidneys (Zachos et al., 2005). NHE3 channels are highly expressed on the apical regions of enterocytes, whereas related the related sodium hydrogen exchanger 2 (NHE2) channels are more heavily expressed on the apical side (Barbry and Hofman, 1997). This gives tenapanor a unique ability to regulate sodium levels at the point where we
Increased intracellular calcium triggers the activation of calpain. Calpain, a calcium dependent proteolytic enzyme begins apoptosis (Momeni, 2011). Apoptosis occurs because calpain degrades the membrane, cytoskeleton, and the cell’s DNA. Calpain, in the presence of calpastatin, an endogenous inhibitor protein, unregulates calpain activation (Momeni, 2011). Calpain consists of a two catalytic subunits; within the 80kD subunit there are four domains, domains I through IV. Domains for calcium binding are found in first four EF-hands; the fifth EF-hand goes around the subunits thus creates a heterodimer interface (Todd, Moore, Deivanayagam, Lin, Chattopadhyay, Maki, Wang, & Narayana, 2003). During activation, domain I hydrolyses other proteins and these proteins go from the 80kD subunit to 30kD subunit (Suzuki, Hata, Kawbata, & Sorimachi 2004). After that, the active site cleft is rearranged because two calcium atoms bind (Suzuki, Hata, Kawbata, & Sorimachi
Second, in order to further confirm the information about characteristics and function of the targeting protein that we have
More than five million are living with Alzheimer’s disease in the United States and the number is set to almost triple by the year 2050. It is common in the elderly and generally occurs in persons over 65 years of age, but early onset of Alzheimer’s has also been documented (“Alzheimer’s disease facts,” 2016, para. 1). It starts in the medial temporal area of the brain, usually in the hippocampus, and then spreads to other areas of the brain. Blows (2011) explains, “Alois Alzheimer was a German psychiatrist who in 1906 described a dementia with two specific changes found in the brain after death... these changes were the presence of extracellular plaques and intracellular neurofibrillary tangles and these became the hallmarks of this disease” (p. 286). Loss of neurons takes place and amyloid plaques form. This is due to build-up of non-functioning proteins and can be observed by imaging techniques (Radin, 2003, p. 41). There are many risk factors that increase the risk of Alzheimer’s disease. The greatest risk factor is family history, but other risk factors include diabetes, hypertension obesity, hyperlipidemia, smoking, depression, physical inactivity, low estrogen levels, and head trauma (Huether & McCance, 2014, p. 546). The actual cause of Alzheimer’s is unknown, but there are genes associated with it that make the disease heritable. What is clear is that
Although a rare form of diabetes, neonatal diabetes is a significant condition. It is referred to as neonatal because it has a usual onset in neonates, and is characterized by impaired ability to release insulin, although it is still produced. This is mainly related to mutations in the KCNJ11/SUR1 channel. In normal physiology, closing of this channel in response to a shift in [ATP]/[ADP] ratio causes a cascade that results in the release of insulin. Several amino acid residue mutations have been linked to this disorder. Although mutations in KCNJ11 are better understood, mutations in SUR1 can be equally as disruptive to normal function. In addition, KCNB1 and other channels working through a similar mechanism can effect the release of insulin,
consists of ComP, the histidine kinase, and ComA, the response regulator.2 There are two known
In vitro: A non-toxic concentration of enniatin B could strongly inhibit a Pdr5p-mediated efflux of cycloheximide or cerulenin in Pdr5p-overexpressing cells. The mode of Pdr5p inhibition caused by enniatin B was competitive against FK506. However, enniatin B could not inhibit the function of Snq2p, a homologue of Pdr5p [1]. Another study showed that enniatin B was a relatively poor ionophore that could facilitate import of K+ and Na+ across membranes [2]. It was also found that like other enniatins, enniatin B was able to inhibit acyl-CoA: cholesterol acyltransferase [3].
These two hormones allow the regulation and correct absorption of calcium. The parathyroid hormone will increase when calcium levels when they are low. In turn, this will release Vitamin D (from the kidneys) to increase absorption in the intestines (Postman, 1998; Redrobe, 2002). Calcitonin is produced whenever calcium levels are high. Calcitonin increases the absorption of calcium into the bones and out of the blood stream (Postman, 1998; Redrobe, 2002). See Figure 1 for schematic of this regulation. Finally, mammals generally excrete calcium through
Chymotrypsin is a digestive enzyme component of pancreatic juice acting in the duodenum where it performs proteolysis, the breakdown of proteins and polypeptides. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond (the P1 position) is a largehydrophobic amino acid (tyrosine, tryptophan, and phenylalanine). These amino acids contain an aromatic ring in their sidechain that fits into a 'hydrophobic pocket' (the S1 position) of the enzyme. It is activated in the presence of trypsin. The hydrophobic and shape complementarity between the peptide substrate P1 sidechain and the enzyme S1 binding cavity accounts for the substrate specificity of this enzyme. Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates, particularly those containing leucine and methionine at the P1 position.
Tryptophan is one of the scarcest amino acids found in nature and is fundamental to most proteins found throughout vertebrates. This amino acid is crucial for sufficient growth in infants and to maintain nitrogen balance in adults. The IUPAC name for tryptophan is (2S)-2-amino-3-(1H-indol-3-yl) propanoic acid and this amino acid is often abbreviated as “Trp” or “W.” Amino acids are a vital component of living organisms and act as building blocks for proteins. The basic structure of an amino acid consists of a hydrogen atom, an amino group, a carboxyl group, and an “R” group attached to a central carbon. The structure of the “R” group determines the function and interaction properties of the amino acid. There are twenty common amino acids that are found within the proteins of the human body, Tryptophan is one of them. Although amino acids are structural components of proteins, these macromolecule subunits are also catabolized into products that serve vital roles within the body. Tryptophan is catabolized into the serotonin, kynurenine, and plays a role in NAD/NADP synthesis. There are also various metabolic diseases that are associated with amino acid, caused by deficiencies and the inability to catabolize/metabolize specific amino acids. Familial hypertryptophanemia and pellagra are metabolic disorders associated with tryptophan.
by an elaborate system of controls to provide for fundamental processes (Marieb & Hoehn 2010). Calcium is the most abundant cation found in human bodies, vital to normal function of a host of processes including: nerve excitability, hormone secretion, blood clotting, taste transduction, muscle function and cellular adhesion (Hutchins 2014). This essay will outline some of the more important roles of calcium metabolism. The essay will begin by discussing how calcium provides
Defensins are also small, cysteine-rich and cationic peptide which are consisting of 18-45 amino acids with 6-8 cysteine residues and they form disulfide bridges. Due to the differences in alignment of disulfide bond and molecular structure, two subclasses can be found in human. They are alpha defensins and beta defensins. Human alpha defensins are also called human neutrophil peptides and have four subtypes such as, HNP1, HNP2, HNP3 and HNP4 which are 29-35 amino acids long. First three subtypes