Tutor profile: Allison M.
Subject: Biomedical Science
What is the difference between tumor-specific antigens and tumor-associated antigens?
Tumor antigens refer to antigens that can be detected on tumor cells, and are recognized by the immune system as non-self. Compared to normal body cells, tumor-specific antigens (TSAs) refer to antigens which are found ONLY on tumor cells, and these antigens themselves are variable amongst individuals with the same types of cancer. In many cases these TSA are specific antigens called neoantigens, which are either mutated self-proteins or viral proteins which are oncogenic. Meanwhile, tumor-associated antigens (TAAs) refer to antigens which can be found both tumor cells AND certain normal cells. What makes these antigens tumor-associated is that, while the antigen itself is the same, the expression pattern of that particular antigen is different on tumor cells. One such case is that tumor cells express a TAA antigen at "normal," levels, however it is expressed under conditions where it should not be expressed (indicating a loss of gene regulation). Another case is that, while the expression level per cell is normal, the presentation on tumor cells results in an abnormally high number of cells presenting that antigen than under normal cellular conditions.
In glycolysis, steps such as the conversion of glucose to glucose-6-phosphate have a positive change in Gibbs free energy and are therefore considered 'non-spontaneous.' How is it that, in the cell, these reactions are able to proceed 'spontaneously?'
In glycolysis, non-spontaneous processes such as glucose to glucose-6-phosphate are able to proceed under cellular conditions because they are COUPLED with a highly spontaneous process, which results in an overall net negative change in Gibbs free energy. In this particular example, the conversion of glucose into glucose-6-phosphate is coupled with the metabolism of ATP into ADP (facilitated by hexokinase), a process which is very favorable and has a very negative change in Gibbs free energy. This results in a net negative change in Gibbs-free energy, enough to overcome the non-spontaneity and proceed under cellular conditions.
What does it mean for a channel protein to be 'selectively' permeable, and what determines this selectivity?
Channel proteins make up a specific type of membrane proteins that function in the facilitation of passive transport across cell membranes. The higher order protein structure is such that it forms a 'pore' in the cell membrane through which ions/molecules are able to pass as they flow down their concentration gradient. However, not just any particle can pass through any channel; most channels are selective, meaning that only a specific ion/molecule is able to cross the membrane through the channel. This selectivity is ultimately determined by two major factors: the shape of the overall protein itself, and the R groups of the amino acids present on the pore-side of the channel. The overall tertiary (and/or quaternary} structure of the channel protein itself determines which particles are able to pass through the protein, simply based on physical size alone. In terms of the other properties of the diffusing particles, the ability to pass through the channel is dictated by the presence of charged or uncharged polar R groups lining the inside of the protein pore. The particular arrangement of these R groups will act more favorable with certain particles more than others, especially ions (such as potassium), and it is these particular interactions which can determine whether or not it is favorable for that particle to continue to interact with the present R groups as it passes through the inner pore. It is also the interactions with these R groups which contributes to conformational changes in the channel protein upon the selected particle entering the pore, which enables the 'selected' ion/molecule to pass through the channel while preventing others from flowing through.