By B. Achmed. Erskine College.

The unique characteris- portion of DNA that encodes a functional tics of a protein are dictated by its linear sequence of amino acids prednisolone 40 mg generic allergy medicine and erectile dysfunction, termed its pri- product discount prednisolone 10mg amex allergy treatment with laser, such as a polypeptide chain. Muta- tions, which are changes in the nucleotides in mary structure. The primary structure of a protein determines how it can fold and a gene, result in a change in the products of how it interacts with other molecules in the cell to perform its function. The geneti- mary structures of all of the diverse human proteins are synthesized from 20 cally inherited disease sickle cell anemia is, for amino acids arranged in a linear sequence determined by the genetic code. Each of the amino acids used for protein encoding one of the subunits of hemoglobin. It contains a carboxylic acid Hemoglobin is the protein present in red group, an amino group attached to the -carbon in an L configuration,ahydro- blood cells that reversibly binds O2 and trans- gen atom, and a chemical group called a side chain that is different for each ports it to tissues. In solution, the free amino acids exist as zwitterions, ions in which tein comprises four polypeptide chains, 2 the amino group is positively charged and the carboxylate group is negatively and 2. In proteins, these amino acids are joined into linear polymers called structure (i. Sickle cell anemia is caused by a one amino acid and the amino group of the next amino acid. The chemical properties of the side chain determine the types of bonds and tamic acid to a valine. Thus, amino acids are often grouped by polarity of the side chain (charged, 2 1 nonpolar hydrophobic,oruncharged polar) or by structural features (aliphatic, cyclic, or aromatic). The side chains of the nonpolar hydrophobic amino acids (alanine, valine, leucine, isoleucine, phenylalanine, and methionine) cluster together to exclude water in the hydrophobic effect. The uncharged polar amino acids (serine, threonine, tyrosine, asparagine, and glutamine) participate in hydro- gen bonding. Cysteine, which contains a sulfhydryl group, forms disulfide bonds. Heme groupHeme group The negatively charged acidic amino acids (aspartate and glutamate) form ionic (electrostatic) bonds with positively charged molecules, such as the basic amino acids (lysine, arginine, and histidine). The charge on the amino acid at a particular pH is determined by the pKa of each group that has a dissociable proton. Mutations in the genetic α2 α1 code result in proteins with an altered primary structure. Mutations resulting in single amino acid substitutions can affect the functioning of a protein or can con- fer an advantage specific to a tissue or a set of circumstances. Many proteins such as hemoglobin exist in the human population as polymorphisms (genetically determined variations in primary structure. The primary structure of some proteins, such as creatine kinase, can also vary between tissues (tissue-specific isozymes) or between intracellular locations in the same tissue. Electrophoretic separation of tissue-specific isozymes has been useful in medicine as a means of identifying the tissue site of injury. In addition to the amino acids encoded by DNA that – Carboxyl COO group form the primary structure of proteins, many proteins contain specific amino acids Amino + that have been modified by phosphorylation, oxidation, carboxylation, or other H3N C H group reactions. When these reactions are enzyme-catalyzed, they are referred to as α-Carbon R post-translational modifications. General structure of the amino acids found in proteins. THE WAITING ROOM Will Sichel is a 17-year-old boy who came to the hospital emergency room with severe pain in his lower back, abdomen, and legs, which began after a 2-day history of nausea and vomiting caused by gastroenteritis. He was diagnosed as having sickle cell disease at age 3 years and has been admitted to the hospital on numerous occasions for similar vaso-occlusive sickle cell crises. On admission, the patient’s hemoglobin level in peripheral venous blood was 7. The hematocrit or packed cell volume (the percentage of the total volume of blood made up by red blood cells) was 23. His serum total bilirubin level (a pigment derived from hemoglobin degradation) was 2. An x-ray of his abdomen showed radiopaque stones in his gallbladder. With chronic hemolysis (red blood cell destruction), the amount of heme degraded to bilirubin is increased. These stones are the result of the chronic excretion of excessive amounts of bilirubin from the liver into the bile, leading to bilirubinate crystal deposition in the gallbladder lumen. Cal Kulis is an 18-year-old boy who was brought to the hospital by his The term calculus is used to mother because of the sudden onset of severe pain in the left flank radiat- describe any abnormal concretion ing around his left side toward his pubic area. His urine was reddish-brown (concrete-like precipitate) of min- eral salts.

Protein- uria is usually mild if the immune response is self-limited order prednisolone 5mg with mastercard allergy medicine like singular. Overall order prednisolone 10mg line allergy-x for dogs reviews, one of the most useful clinical indicators of glomerular filtration rate in both health and disease is the serum creatinine concentration. The endogenous production of creatinine, which averages approximately 15 mg/kg of body weight per day, is correlated with muscle mass and, therefore, tends to be constant for a given individual if renal function is normal. Any rise in serum creatinine in patients such as Rena Felya, therefore, can be assumed to result from decreased excretion of this metabolite into the urine. The extent of the rise in the blood is directly related to the severity of the pathologic process involving the glomerular units within the kidneys. BIOCHEMICAL COMMENTS The SERCA pump is a transmembrane protein of 110 kDa present in several different isoforms throughout the body. Three genes encode SERCA proteins, designated SERCA1, SERCA2, and SERCA3. The SERCA1 gene produces two alternatively spliced transcripts, SERCA1a and SERCA1b. SERCA1b is expressed in the fetal and neonatal fast-twitch skeletal muscles, and is replaced by SERCA1a in adult fast-twitch muscle. The SECA2 gene also undergoes alternative splicing, producing the SERCA2a and SERCA2b isoforms. The SERCA2b isoform is expressed in all cell types and is associated with inositol trisphosphate (IP3)-regulated calcium stores. SERCA2a is the primary isoform expressed in cardiac tissue. SERCA3 produces at least five different alternatively spliced isoforms, which are specifically expressed in different tissues. SERCA2a plays an important role in cardiac contraction and relaxation. Contrac- tion is initiated by the release of calcium from intracellular stores, whereas relaxation CHAPTER 47 / METABOLISM OF MUSCLE AT REST AND DURING EXERCISE 879 occurs as the calcium is re-sequestered in the sarcoplasmic reticulum, in part mediated by the SERCA2a protein. The SERCA2a pump is regulated, in part, by its association with the protein phospholamban (PLN). PLN is a pentameric molecule consisting of five identical subunits of molecular weight 22,000 Daltons. PLN associates with SERCA2a in the sarcoplasmic reticulum and reduces its pumping activity. Because new contractions cannot occur until cytosolic calcium has been re-sequestered into the sarcoplasmic reticulum, a reduction in SERCA2a activity increases the relaxation time. However, when called on, the heart can increase its rate of contractions by inhibiting the activity of phospholamban. This is accomplished by phosphorylation of phospho- lamban by protein kinase A (PKA). Epinephrine release stimulates the heart to beat faster. This occurs through epinephrine binding to its receptor, activating a G protein, which leads to adenylyl cyclase activation, elevation of cAMP levels, and activation of protein kinase A. PKA phosphorylates PLN, thereby reducing its association with SERCA2a and relieving the inhibition of pumping activity. This results in reduced relaxation times and more frequent contractions. Mutations in PLN lead to cardiomyopathies, primarily an autosomal dominant form of dilated cardiomyopathy. This mutation leads to an arginine in place of cysteine at position 9 in PLN, which forms an inactive complex with PKA and blocks PKA phosphorylation of PLN. Individuals with this form of PLN develop cardiomyopathy in their teens. In this condition, the cardiac muscle does not pump well (because of the constant inhibition of SERCA2a), and becomes enlarged (dilated). Because of the poor pumping action of the heart, fluid can build up in the lungs. The pulmonary congestion results in a sense of breathless- ness (left heart failure). Eventually, progressive left heart failure leads to fluid accumulation in other tissues and organs of the body, such as the legs and ankles (right heart failure). Malonyl CoA control of fatty acid oxidation in the ischemic heart. Muscle Metabolism in Metabolic Regulation in Mammals. Phospholamban: a crucial regulator of cardiac contractility.

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The suffix “ine” denotes the presence of nitrogen (amine) in the ring generic prednisolone 20 mg otc allergy medicine safe for dogs. Chemi- 6 cal modifications often occur in the liver 40 mg prednisolone fast delivery allergy drops, kid- The pyrimidine uracil is an exception to this general type of nomenclature. The util- ney, or other tissues that inactivate or detox- ity of these nitrogen-containing ring structures lies in the ability of the nitrogen to ify the chemicals, make them more form hydrogen bonds and to accept and donate electrons while still part of the ring. Uric acid, the basis of uted equally among all six carbons (see Fig. Judging from the simi- larity in structure, do you think it is derived 2. NUCLEOSIDES AND NUCLEOTIDES from the degradation of purines, pyrim- idines, or pyridines? A nucleoside consists of a nitrogenous base joined to a sugar, usually ribose or deoxyribose, through an N-gly- cosidic bond (see Fig. If phosphate groups are attached to the sugar, the com- Cholesterol is composed almost pound becomes a nucleotide. In the name of the nucleotide adenosine triphosphate entirely of CH2 groups and is there- fore water-insoluble. Estradiol is (ATP), the addition of the ribose is indicated by the name change from adenine to likewise relatively water-insoluble. Monophosphate, diphosphate, or triphosphate cholic acid contains a hydrophilic carboxyl are added to the name to indicate the presence of 1, 2, or 3 phosphate groups in the group, and three hydroxyl groups. The structures of the nucleotides that serve as precursors of DNA and by the dashed lines, the three hydroxyl RNA are discussed in more detail in Section Three, Chapter 12. TAUTOMERS In many of the nitrogen-containing rings, the hydrogen can shift to produce a tau- Lotta Topaigne’s gout is caused by tomer, a compound in which the hydrogen and double bonds have changed position depositions of monosodium urate (i. Tautomers are considered the same crystals in the joint of her big toe. For example, in the two tautomeric dissociated a proton to form urate, which is forms of uric acid, a proton can dissociate from the enol form to produce urate. In the more acidic urine gener- ated by the kidney, the acidic form, uric acid, V. FREE RADICALS may precipitate to form kidney stones. Radicals are compounds that have a single electron, usually in an outer orbital. Free radicals are radicals that exist independently in solution or in a lipid environment. Purines Pyrimidine Pyridine NH2 O O O C N C N C C N 6 C 7 HN C HN 4 1 5 3 5 3 OH 8CH CH HC2 4C 9 C C C2 6CH 3 N H N N 1 + N 2 N O N N H H Adenine (A) Guanine (G) Thymine (T) Nicotinic acid Fig. They are Many of the compounds in the body are capable of being converted to free rad- involved in all chronic disease states (e. Radiation, coronary artery disease, diabetes mellitus, for example, dissociates water into the hydrogen atom and the hydroxyl radical: arthritis, and emphysema) as well as acute injury (e. Through H2O 4 H• OH• free radical defense mechanisms in our cells, we can often restrict the damage attributed to In contrast, water normally dissociates into a proton and the negatively charged the “normal” aging process. The hydroxyl radical forms organic radicals by taking one electron (as H•) from a compound such as an unsaturated membrane lipid, which then has a single unpaired electron and is a new radical. Uric acid contains two rings and is Compounds that are radicals may be written with, or without, the radical show- similar to the purines adenine and ing. For example, nitrogen dioxide, a potent, reactive, toxic radical present in smog guanine (adenine is shown in Fig. In fact, it is the urinary excretion prod- than NO •. Superoxide, a radical produced in the cell and that is the source of much 2 uct formed from the oxidation of these two destruction, is correctly written as the superoxide anion, O2. It is not very soluble in water, size its free radical nature, the same compound is sometimes written as O2 •. If a particularly if the pH is near the pKa of its compound is designated as a radical in the medical literature, you can be certain that acidic OH group. If present in excess amounts, Na urate tends to precipitate in it is a reactive radical, and that its radical nature is important for the pathophysiol- joints, causing the severe pain of gout expe- ogy under discussion. The reduc- CLINICAL COMMENTS ing sugar test was used for detection of sugar in the urine long before spe- Dianne Abietes. The severity of clinical signs and symptoms in cific enzymatic assays for glucose and galac- patients with diabetic ketoacidosis (DKA), such as Di Abietes, is directly tose became available. In this test, the aldehyde correlated with the concentration of ketone bodies in the blood. Direct group of a sugar is oxidized as it donates elec- quantitative methods for measuring acetoacetate and -hydroxybutyrate are not rou- trons to copper; the copper becomes reduced and produces a blue color.

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Outcome of Treatment Pain from high stress in the extensor mechanism is usually short term and resolves with activity limitations purchase 40mg prednisolone with visa allergy medicine safe during pregnancy. For children with significant crouched gait generic 5 mg prednisolone overnight delivery allergy forecast temple tx, correction of the primary etiology of the crouch will almost always resolve the pain from the stress reaction. Although radiographic evidence of patella alta and fragmentation apophysitis is common, surgical treatment is rarely required. Also, there are no data from postoperative gait evaluations. With current understanding of the etiology of crouched gait, the need for femoral exten- sion osteotomy and plication of the patellar ligament is required only in rare 692 Cerebral Palsy Management Figure 11. This 12-year-old girl with diple- gia was growing rapidly and complaining of knee pain. On physical examination she had popliteal angles of 60° and a positive Ely test at 100°. She was tender over the patella, es- pecially the distal pole. Her gait was remark- able only for a mild crouch gait. The radio- graph demonstrated a stress fracture of the patella with a stress reaction of the distal pole. She was given instructions on hamstring and quadriceps stretching and given a pair of solid-ankle AFOs with a wide anterior tibial strap to improve the effectiveness of the plantar flexion knee extension couple. This orthotic unloaded the knee extensors and the pain rapidly decreased. The AFO wear was continued for 1 year, then she was again weaned from the orthotic, and she has re- neglected cases, making it difficult to accumulate enough cases to understand mained pain free for the past 5 years. Complications of Treatment The primary complications of treating painful stress reactions is the prolonged nature of the pain (Figure 11. This pain may require prolonged physical therapy for stretching and strengthening exercises of the knee extensor mech- anism. Acute disruption of the stress fracture can occur, but is rare. If acute disruption occurs, the displacement has to be repaired surgically. Complications of treating the extensor lag by surgical plication are mainly due to excessive shortening and not removing the rectus muscles from the quadriceps tendon. These complications may lead to a severe stiff knee in swing phase and even a fixed knee extension contracture. After the extensor mechanism has been tightened, the knee should be able to flex easily to 90° intraoperatively. The extensor muscles cannot be stretched if only 45° of flexion is present after patellar plication. These extension contractures are dis- abling, especially from knee stiffness in swing phase, and may cause prob- lems with sitting and with coming to standing from a sitting position. Fixed Knee Extension Contractures A mild to moderate fixed knee extension contracture, which allows knee flexion past 90°, is common but almost never of any clinical consequence. Usually, the severe contracture limits motion to less than 30° to 40° of knee flexion and is very disabling, especially impairing seating. Only rarely does a severe extension contracture occur spontaneously in individuals who can stand or walk. In rare situations, with individuals who can stand or walk, the extension contracture causes great difficulty in coming to stand. Usually, these individuals require some help or lifting to come to the standing posi- tion. In almost all severe extension contractures, the primary contracture occurs in the vastus muscles, and the rectus is relatively less contracted because there is a combination of hip and knee extension contractures in most cases. The treatment of severe knee extension contracture is a Z-lengthening of the quadriceps tendon. In individuals who can stand and walk, a V–Y-lengthening is preferred to allow better maintenance of continuity of the tendon. At least 90° of knee flexion should be obtained at the time of the lengthening. The postoperative management must include 8 to 12 hours per day of splinting the knee in flexion with some passive knee range of motion every day. In most individuals, 70° to 90° of knee flexion is preserved after full rehabilitation 11.

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