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there are 6 questions that need to be answered – minimum 150 words for each (5-10 sentences) = TOTAL minimum 1000 wordsMAKE SURE YOU DON’T COPY FROM INTERNET AND ONLY USE OWN WORDS – MUST BE SCIENTIFIC STYLE PAPER each question should be about 5-10 sentences (minimum 150 words)each of the bullet points are questions. Each question can be listed then answered underneathHemoglobin (Hb) is the essential O2 transporter in adult humans that carries oxygen from the lungs to peripheral tissues where it is needed for oxidative respiration.As you might imagine, amino acid substitutions in Hb that lead to dysfunction can have rather significant physiological effects. Perhaps surprisingly, there are more than 1,000 naturally occurring Hb variants (Hb genes that encode proteins with amino acid substitutions) that alter its structure and biochemical properties resulting in mild to severe pathologies. In addition, tissue, organismal, and developmental stage specific Hb can be expressed to suit the needs of the organism. Here you will explore an Hb variant of your choosing and discuss the biochemical effects of this substitution on: 1) Hb-O2 binding affinity and cooperativity, 2) allostery, 3) and human physiology.Please respond to each of the following items thoroughly, but concisely. Most of the questions have multiple parts; be sure to provide an answer for each of them. An excellent response will include details from the literature and course content to accurately describe the effect of your amino acid substitution on Hb function and physiology.Please provide your response directly on this document. The amount of space provided for each question does not reflect the suggested amount of space needed to provide an excellent response. Please provide references for any relevant information that you obtain from the literature.(5 Points) Please choose an Hb variant from the literature. This should be a variant that has been characterized biochemically and physiologically (and perhaps structurally). This can include a naturally occurring Hb that contains an amino acid substitution, or a tissue or organism specific Hb that displays altered biochemical properties relative to adult human Hb. Please provide the name and a reference for your Hb variant below.
(10 points) Describe how this variant was identified, or what special role it plays in normal physiology.
(5 points) What amino acid substitution does your Hb variant express? Describe the chemical features of the original and variant amino acids.
(10 points) In which region of the Hb tetramer structure does this substitution occur? I.e. at the α1-β1 interface, the α1-β2 interface, the O2 binding pocket, the Heme binding pocket, the hydrophobic core, etc.?Describe how you think this substitution might affect Hb function based on its location in the tetramer structure. How does this relate to topics that we discussed in class regarding Hb function?
(10 points) describe the biochemical effects of your amino acid substitution. I.e. does it lead to a reduction in O2 binding affinity, cooperativity, relaxed allostery, etc.? Do these biochemical effects make sense given what you know about the chemical nature of the substitution and the structure and function of Hb?
(10 points) What is the clinical impact of this substation on human physiology? Is this a severe or mild phenotype? What are the available treatments associated with this variant and what are their mechanisms of action? Please be as detailed as possible here.
LengthYou should be able to provide the necessary information for each question in 5 to 10 sentences (sometime more, sometimes less, but this is a good target). We do not need to write a thesis dissertation, but at the same time, you will want to ensure that you have answered the questions as they are written.Available characterization.It may that the Hb variant you choose has been well characterized biochemically, but there is no information about its clinical effects. Conversely, you may find a variant has been studied quite extensively in the clinic, but there is little information available regarding its biochemistry (O2 affinity, allostery, cooperativity, etc.).If this is the case I would prefer you choose a variant that has been extensively characterized biochemically. This way you should be able to address questions 1-5.IMPORTANT: If you are unable to provide information for #6 regarding your specific Hb variant because it isn’t available, please provide information about general Hb mutant phenotypes. With what type of pathology could patients present (generally) and what are some general treatments. You also have the option of finding an additional Hb variant that has been clinically characterized to answer question # 6. This is not mandatory, but it will be looked on favorably when your responses are evaluated.ScopeI am really looking for you to relate the content learned throughout the course to the “real world” research being done on Hb. Thus, you don’t have to describe every experiment ever done on your Hb variant. I will be evaluating your understanding of the literature based on what we have discussed about Hb in class (or through the videos). Be as thorough as possible, but it is not necessary to try to describe concepts that we did not address in class.Literature and referencesTo begin, I would recommend searching for a review article that discusses Hb variants and their classes. You could use a scientific database like pubmed or scopus (have you been shown how to use these databases in your undergraduate careers?), or you could just do a google search. From the review article, you should be able to focus your efforts on a particular Hb variant that interests you by looking at the references in the review. I have linked to one review article below that might get you started.You could also look in a textbook. There are some Hb variants that are commonly discussed in texbooks. You will need to find at least one additional resource if you use a textbbok.Please provide a reference for any resource that you use (including a textbook). Typically you will only need to provide the author(s), title, year of publication, and journal or book title. Don’t worry about format for this exercise.Review article – This is a bit older (2013) – you may be able to find something more current – Hemoglobin Variants: Biochemical Properties and Clinical Correlates1. (5 Points) Please choose an Hb variant from the literature. This should be a variant that has been characterized biochemically and physiologically (and perhaps structurally). This can include a naturally occurring Hb that contains an amino acid substitution, or a tissue or organism specific Hb that displays altered biochemical properties relative to adult human Hb. Please provide the name and a reference for your Hb variant below.
2. (10 points) Describe how this variant was identified, or what special role it plays in normal physiology.
3. (5 points) What amino acid substitution does your Hb variant express? Describe the chemical features of the original and variant amino acids.
4. (10 points) In which region of the Hb tetramer structure does this substitution occur? I.e. at the α1-β1 interface, the α1-β2 interface, the O2 binding pocket, the Heme binding pocket, the hydrophobic core, etc.?Describe how you think this substitution might affect Hb function based on its location in the tetramer structure. How does this relate to topics that we discussed in class regarding Hb function?
5. (10 points) describe the biochemical effects of your amino acid substitution. I.e. does it lead to a reduction in O2 binding affinity, cooperativity, relaxed allostery, etc.? Do these biochemical effects make sense given what you know about the chemical nature of the substitution and the structure and function of Hb?
6. (10 points) What is the clinical impact of this substation on human physiology? Is this a severe or mild phenotype? What are the available treatments associated with this variant and what are their mechanisms of action? Please be as detailed as possible here.
for example under question 2, you would write the paragraph to that question

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