Biochemistry Sheet 27, 2024- PDF

27 Nahla Ayad Layan Alnaimat Nafez Abutarboush 1  Plasma proteins ❖Prealbumin (transthyretin): Prealbumin is not immature version of albumin as the immature version will have pro in its name. Prealbumin is another protein that is also called tran...

27 Nahla Ayad Layan Alnaimat Nafez Abutarboush 1  Plasma proteins ❖Prealbumin (transthyretin): Prealbumin is not immature version of albumin as the immature version will have pro in its name. Prealbumin is another protein that is also called transthyretin, which is the protein responsible for transporting thyroid hormones (T4(thyroxine and T3)). It is called prealbumin as it migrates (runs) ahead of albumin in gel electrophoresis. It is a small glycoprotein with molecular weight of 62 kDa, it is rich in tryptophan and has 0.5% carbohydrates. It is low in blood level = 0.25g/l. It has a short half-life of 2 days, making it useful in medical testing for diagnosing diseases or poor protein nutrition. It can also be used for liver function tests, but it is less reliable due to its low concentration in the blood. ❖Globulins 2 1. Alpha 1 globulins: Alpha1-Antitrypsin (A1AT): Alpha1-antitrypsin neutralizes trypsin and trypsin-like enzyme actions, which are proteolytic enzymes that break down proteins. It is also referred to as Alpha1-Antiproteinase because it inhibits a wide range of proteases. Molecular Weight: 53 kDa. Plasma Concentration: It constitutes about 90% of the Alpha-1 globulin fraction in serum protein electrophoresis. Polymorphism: It is a polymorphic protein with over 75 known forms. The most common form is the MM phenotype, encoded by the PiM PiS, PiZ, and PiF alleles. Genetic Deficiency: Individuals with the ZZ genotype (the worst one ) have the most severe deficiency, leading to a 10% reduction in A1AT activity and a high risk of emphysema. The SZ genotype is also associated with deficiency, particularly when no M copy is present, resulting in reduced or defective A1AT activity MS,MZ usually not affected. Role in Elastase Regulation: Alpha1-antitrypsin inhibits elastase, an enzyme produced by macrophages during inflammation to break down elastic fibers and allow immune cells to access sites of infection or injury. If not regulated by A1AT, elastase can cause excessive tissue damage. 3  Acute Phase Protein: Alpha1-antitrypsin is an acute-phase protein, meaning its concentration increases during inflammation, cancer, or trauma as part of the body’s response to these conditions. The most common cause of lung inflammation is smoking. Smoking induces chronic inflammation, which results in the continuous presence of macrophages and increased production of elastase. Oxidation of Alpha1-Antitrypsin: Smoking can oxidize the methionine-358 (Met-358) residue located on the surface of alpha1-antitrypsin. Methionine, a nonpolar amino acid, can be oxidized to methionine-sulfoxide under harsh conditions. This oxidation prevents alpha1-antitrypsin from binding to elastase, rendering it unable to inhibit elastase activity effectively. Pathophysiology of Emphysema: Without proper inhibition, elastase breaks down the walls of the alveoli, reducing the surface area available for gas exchange. This leads to the formation of larger air spaces in the lungs, causing the characteristic barrel chest seen in emphysema patients. 4  Impact on PiZZ Individuals: The situation is particularly severe in patients with the PiZZ genotype, as they already have a significant deficiency in functional alpha1- antitrypsin. Smoking further exacerbates their condition by both increasing elastase activity and oxidizing the remaining functional alpha1-antitrypsin, leading to rapid disease progression and severe complications. Alpha1-antitrypsin is produced in the liver, but mutations in its gene can alter the protein’s shape, leading to aggregation. In the ZZ phenotype, the defective protein forms clumps in the liver due to interactions between its loops and beta sheets. This can cause liver damage, with about 10% of ZZ individuals developing cirrhosis. b)Alpha1- fertoprotein: is synthesized in the yolk sac of the fetus then by liver parenchyma cells, not supposed to increase in Concentration of adults only in one case which is in pregnancy for pregnant women or when there is cancer in the liver including hepatoma and acute hepatitis (cells breakdown so product of them leaves the cell). They associated it with Down’s syndrome if there is low levels of it. It protects the fetus from immunologic attacks, modulates the growth of fetus and transports compounds such as steroids. 5  2. Alpha 2 globulins: a). Haptoglobin (HP): it is also an acute phase protein, its molecular weight is 90 kDa. It is a tetramer that has 3 phenotypes: 1. Hp1-1: alpha1,alpha1 + 2beta 2.Hp2-1: alpha1-alpha2+ 2beta 3. Hp 2-2: alpha2,alpha2 + 2beta Its function is to bind to free hemoglobin, When hemolysis occurs haptoglobin binds to it to prevent the loss of hemoglobin and iron to be recycled and not be loss in urine as when combined together it makes a big protein therefor cannot exit the renal circulation. The half life of Hp alone is 5 days however once it binds to hemoglobin its half life becomes shorter and becomes 90 minutes. Within the 90 minutes it will be broken down in the liver and the iron will be extracted to become recycled, this makes it an iron reservation process and decreases level in hemolytic anemia. b). Ceruloplasmin: Ceruloplasmin is a 160 kDa copper-containing glycoprotein that stores copper and regulates its levels in circulation, with each molecule binding up to six copper ions. While 90% of copper in the blood is bound to ceruloplasmin, about 10% is transported by albumin. Copper in tissues is regulated by metallothioneins. In 6 Wilson’s disease, a genetic liver disorder, ceruloplasmin levels may be low or defective, leading to excess copper in the blood and deposits in tissues, causing a copper-like skin discoloration. Treatment involves dialysis to manage copper levels. A ferroxidase: oxidizes ferrous to ferric(transferrin) 3-Beta globulins: C-reactive protein (CRP): A protein that works against the C fraction in the cell wall of a microorganism that is pneumococci and helps in defense against bacteria and foreign substances. It is the main acute phase inflammatory protein, used in all hospitals. Level should be less than 5 if higher means that there is a problem like acute rheumatic fever, bacterial infection, gout and tissue damage. It’s level reaches a peak after 48 hours of incident making it have a monitoring marker. 7 Diseases: If someone has a problem in the kidneys and renal failure so proteins leave the circulation and not restored. Making all of the proteins bands in circulation low. Most plasma proteins are synthesized in the liver except for gamma globulins. In liver diseases proteins are not synthesized so the band will all be low except for the gamma globulins high as they are synthesized somewhere else. When there is a sharp increase in gamma globulin band means that there is cancer affecting them so a patient has myeloma. 8 ‫‪IN THE EXAM:‬‬ ‫المواد بتتراكم ومش‬ ‫ملحق محاضرات بس إنت‬ ‫‪chill guy‬‬ ‫رايق ومتأكد أنك رح‬ ‫تعوض بالفاينل‬ ‫تمت كتابة هذا الشيت عن روح والدة زميلنا عمرو رائد من دفعة تيجان‬ ‫دعواتكم لها بالرحمة والمغفرة‬ ‫‪9‬‬