Using Changes in Glycosylation Patterns as a Biomarker in Autoinmune Diseases and Cancer

In the United States, colorectal cancer affecting both men and women ranks high as a fatal cancer in individuals older than 50 years old (Gould & Dyer, 2011, p. 426). It was estimated in 2011 that 135,260 people diagnosed with colorectal cancer and 51,783 deaths ("Statistics," 2014). With an improved preventive measure of an early detection of precancerous lesions such as polyps, the prevalence of colorectal

The branched chain structure of glycogen provides many units for enzymes to attach to making it easier to breakdown, speeding up the process and allowing for the more immediate release of glucose.

In the meanwhile, in the cytoplasm, the hemagglutinin and neuraminidase have undergone glycosylation, polymerization, and acylation. The hemagglutinin, neuraminidase, and the matrix protein two (M2) all travel together to the plasma membrane. There the proteins meet with the other matrix protein (M1), and begin the

Biomolecules are essential to the cell processes of human life. These molecules are broken down into three major components: Saccharides, Lipids, and Peptides, each carrying specific functions for the processes of the body. Saccharides, our focal point in this lab, enhance the synthesis of other biomolecules by supplying them with carbon, form structure in cells and tissues, provide fuel for metabolism, and are responsible for the storage of glucose. Saccharides are further broken down into three biomolecules: Monosaccharides, Disaccharides, and Polysaccharides. Monosaccharides are simple sugars that can be classified as Aldehyde or Ketone. These Monosaccharides can be easily identified with the reaction between the Benedict’s Reagent with

The American Cancer Society estimates that over 100,000 men and women living in the United States will be diagnosed with colon cancer in 2013. Statistically, cancers of the colon and rectum are often combined and referred to as colorectal cancer. This addition brings the total to over 140,000 affected individuals with over 50,000 of these diagnoses resulting in death (American cancer society, 2013). Globally, the impact of this disease reached over one million people in 2008 with over 600,000 deaths attributed to colorectal cancer (Dusek, Maluskova, & Musik, 2013).

Gaucher disease (GD) is an autosomal recessive inborn error in the pathway of sphingolipid catabolism. Biochemically, this disease is characterized by a deficiency of lysosomal β-glucosidase (glucocerebrosidase GCase, E.C.3.2.1.45) enzyme due to the mutation of GBA gene [1]. The natural substrate of this lysosomal enzyme is glucocerebroside (also called glycosylceramide) mainly present on the cytoplasmic face of cellular membranes and on the cell surface. Lysosomal β-glucosidases play a key role in recycling of this substrate by degradation of glucospingolipid from membranes of apoptatic white blood cells and senescent red blood cells. Genetic mutations of GBA gene affect the enzyme`s catalytic activity and stability and results in the storage

This causes glucosylceramide to accumulate in the body. Scientist have been trying to figure out a way to combat this. Eliglustat is that answer. Glycosphingolipid synthesis and degradation relies on glucosylceramide for its base cerebroside to make more complex glycosphingolipid. The glycosphingolipid pathway starts with ceramide and UDP-glucose making glucosylceramide via glucosylceramide synthase which will then be used to make Ceramide via β-glucocerebrosidase and eventually Ganglioside GM2 and GM1. Now on a histology level glucosylceramide accumulate in lysosomal compartment of macrophages which gives rise to foam cells or “Gaucher cells.” Eliglustat blocks glucosylceramide synthase cause a decrease in level of all glucosylaceramide based glycospholipids (J. A. Shayman, 2010).

ECM many attach to the cell through other glycoproteins that then bind to membrane proteins called integrins

Genetic and phenotypic variation is observed between tumors of different tissue and cell types which mainly due to tumor heterogeneity. Heterogeneity is therefore as an important feature of malignant tumor in diverse genetic backgrounds, pathological patterns, differentiation stages, genetic mutation spectrum, transcriptomics and proteomics gene expression profile, et al. It indicates the high complexity and diversity in cancer progression. Tumor heterogeneity and drug resistance are great challenges for precision oncology and are taken account for the process of research and development of new diagnostic methods and further antitumor agents. Tumor heterogeneity is an important prognostic factor which could be manifested with medical imaging.

Cancer glutamine metabolism has been a whole lot complicated to figure it out since there is flexibility of the metabolic systems as well as the number of free nutrients to which the cells have access to simultaneously. The cancer cells in culture are avid consumers of glutamine and metabolize glutamine at higher rates compared to other amino acids. Glucose on the other hand is said to play a crucial role in cancer cell metabolism and glutamine is second and both are needed for proliferating cancer cells for bioenergetics and synthesis of intermediates for macromolecular. The Warbug’s effect states that most cancer cells rely aerobic glycolysis to generate energy for cellular processes which yields less adenosine 5’-triphosphate (ATP). In

Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front Biosci (Elite Ed). 2010; 2: 1184–95.

Glycolysis as it 's latin roots indicate (“glyco-” meaning sugar, and “=lysis” the break down of) is the bisection of glucose, C6H12O6 into two pyruvate, C3H6O3 molecules, or simply a six-carbon compound to a three-carbon compound. In a series of two enzyme catalyzed reactions, two adenosine triphosphates(ATP) each give one of their phosphate

Advanced glycation end products (AGEs) resulted to be strongly correlated to renal microvascular complications via enhanced expression of adhesion molecules, including

As seen in these tumors, it is clear that c-src can be involved with cancer. It had been observed on several occasions that in abnormal tissues as well as cancer cells the level the c-src protein as well as kinase are elevated and furthermore that these levels continue to increase as the level of disease progresses. There was a clear correlation between c-src activity and cancer development. In breast cancer, they found that the c-Src when overexpressed is activated by HER1 interactions and this is what causes the high kinase activity in the cancer cells. As

Glycosylation of T258 and T396 contributes to hemolytic activity- published in Molecular Immunology in 1989, Kontermann and Rauterberg removed 88% of N-linked glycosylation in C9, resulting in an 80% reduction of hemolytic activity. The direct reduction in hemolytic activity following their removal implicated glycosylation as critical to function.3