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NOMENCLATURE CONCERNS WITH ENZYMES METABOLIZING GLYCOGEN Both glycogen phosphorylase and glycogen synthase will be covalently modified to regulate their activity (Fig purchase 100 mg kamagra chewable with amex. When activated by covalent modification order kamagra chewable 100mg without prescription, glyco- gen phosphorylase is referred to as glycogen phosphorylase a (remember a for active) generic kamagra chewable 100 mg with visa; when the covalent modification is removed generic 100 mg kamagra chewable visa, and the enzyme is inactive kamagra chewable 100mg sale, it is referred to as glycogen phosphorylase b. Glycogen synthase, when not covalently modified is active, and can be designated glycogen synthase a or glycogen synthase I (the I stands for independent of modifiers for activity). When glycogen synthase is covalently modified, it is inactive, in the form of glycogen synthase b or glyco- gen synthase D (for dependent on a modifier for activity). REGULATION OF LIVER GLYCOGEN METABOLISM BY INSULIN AND GLUCAGON Insulin and glucagon regulate liver glycogen metabolism by changing the phosphory- lation state of glycogen phosphorylase in the degradative pathway and glycogen syn- thase in the biosynthetic pathway. An increase of glucagon and decrease of insulin during the fasting state initiates a cAMP-directed phosphorylation cascade, which results in the phosphorylation of glycogen phosphorylase to an active enzyme, and the A ATP P Glycogen phosphorylase b Glycogen phosphorylase a (inactive) (active) B ATP P Glycogen synthase I (or a) Glycogen synthase D (or b) (active) (inactive) Fig. The conversion of active and inactive forms of glycogen phosphorylase (A) and glycogen synthase (B). Note how the nomenclature changes depending on the phosphoryla- tion and activity state of the enzyme. CHAPTER 28 / FORMATION AND DEGRADATION OF GLYCOGEN 519 phosphorylation of glycogen synthase to an inactive enzyme (Fig. As a conse- With a deficiency of debrancher quence, glycogen degradation is stimulated, and glycogen synthesis is inhibited. GLUCAGON ACTIVATES A PHOSPHORYLATION CASCADE THAT degraded in vivo only to within 4 residues of CONVERTS GLYCOGEN PHOSPHORYLASE b TO GLYCOGEN the branchpoint. When the glycogen sam- PHOSPHORYLASE a ples were treated with the commercial preparation containing normal enzymes, Glucagon regulates glycogen metabolism through its intracellular second mes- one glucose residue was released for each senger cAMP and protein kinase A (see Chapter 26). However, in the patient’s cell membrane receptor, transmits a signal through G proteins that activates glycogen sample, with the short outer adenylate cyclase, causing cAMP levels to increase (see Fig. The catalytic subunits of protein kinase A are activated by the dissocia- -1,6 branch. Normal glycogen has 8-10 glu- tion and phosphorylate the enzyme phosphorylase kinase, activating it. Phospho- cosyl residues per branch, and thus gives a rylase kinase is the protein kinase that converts the inactive liver glycogen ratio of approximately 9 moles of glucose phosphorylase b conformer to the active glycogen phosphorylase a conformer 1-phosphate to 1 mole of glucose. Regulation of glycogen synthesis and degradation in the liver. Glucagon binding to the glucagon receptor or epinephrine binding to a receptor in the liver activates adenylate cyclase, via G proteins, which synthesizes cAMP from ATP. Protein kinase A activates phosphorylase kinase by phosphoryla- tion. Phosphorylase kinase adds a phosphate to specific serine residues on glycogen phosphorylase b, thereby converting it to the active glyco- gen phosphorylase a. Protein kinase A also phosphorylates glycogen synthase, thereby decreasing its activity. As a result of the inhibition of glycogen synthase and the activation of glycogen phosphorylase, glycogen is degraded to glucose 1-phosphate. The blue dashed lines denote reactions that are decreased in the livers of fasting individuals. As a result of the activation of glycogen phosphorylase, enzyme has been activated or glycogenolysis is stimulated. INHIBITION OF GLYCOGEN SYNTHASE BY ited under fasting conditions (In a PHast, GLUCAGON-DIRECTED PHOSPHORYLATION PHosphorylate). When glycogen degradation is activated by the cAMP-stimulated phosphorylation cascade, glycogen synthesis is simultaneously inhibited. The enzyme glycogen syn- thase is also phosphorylated by protein kinase A, but this phosphorylation results in a less active form, glycogen synthase b. The phosphorylation of glycogen synthase is far more complex than glycogen phosphorylase. Glycogen synthase has multiple phosphorylation sites and is acted on by up to 10 different protein kinases. Phosphorylation by protein kinase A does not, by itself, inactivate glycogen synthase. Instead, phosphorylation by protein kinase A facilitates the subsequent addition of phosphate groups by other kinases, and these inactivate the enzyme.
The com- showed she ate 100 g carbohydrate purchase 100mg kamagra chewable free shipping, plete oxidation of triacylglycerols to CO2 and H2O in the body releases approxi- 20 g protein purchase 100mg kamagra chewable, and 15 g fat each day generic kamagra chewable 100 mg amex. CH2OH CH2OH O O O OH OH O HO HO CH2OH CH2OH CH2 CH2OH O O O C O H H H C C O O O OH H OH OH OH HO OH C C HO HO HO H OH Starch Glycogen Glucose or (Diet) (Body stores) Fig purchase kamagra chewable 100 mg on line. Starch discount 100mg kamagra chewable overnight delivery, our major dietary carbohydrate, and glycogen, the body’s storage form of glucose, have sim- ilar structures. They are polysaccharides (many sugar units) composed of glucose, which is a monosaccharide (one sugar unit). Dietary disac- charides are composed of two sugar units. Palmitate and stearate are saturated fatty acids, i. Polyunsaturated fatty acids have more than one double bond. Alcohol drate, 150 g protein, and 95 g fat each day. In addition, he drank 45 g Many people used to believe that alcohol (ethanol, in the context of the diet) has no alcohol. In fact, ethanol (CH3CH2OH) is oxidized to CO2 and H2O in the body per day? BODY FUEL STORES Although some of us may try, it is virtually impossible to eat constantly. Fortunately, we carry supplies of fuel within our bodies (Fig. These fuel stores are light in weight, large in quantity, and readily converted into oxidizable substances. Most of It is not surprising that our body us are familiar with fat, our major fuel store, which is located in adipose tissue. In addition also store fuels in the form of starch or to our fat stores, we also have important, although much smaller, stores of carbohy- glycogen, triacylglycerols, and proteins. Glycogen CHAPTER 1 / METABOLIC FUELS AND DIETARY COMPONENTS 7 Mr. Applebod consumed Muscle glycogen 585 4 2,340 kcal as carbo- 0. Fuel composition of the average 70-kg man after an overnight fast (in kilograms and as percentage of total stored calories). Body protein, particularly the protein of our large muscle masses, also serves to some extent as a fuel store, and we draw on it for energy when we fast. Fat Our major fuel store is adipose triacylglycerol (triglyceride), a lipid more commonly known as fat. The average 70-kg man has approximately 15 kg stored triacylglycerol, which accounts for approximately 85% of his total stored calories (see Fig. In biochemistry and nutrition, the Two characteristics make adipose triacylglycerol a very efficient fuel store: the standard reference is often the fact that triacylglycerol contains more calories per gram than carbohydrate or pro- 70-kg (154-lb) man. This standard tein (9 kcal/g versus 4 kcal/g) and the fact that adipose tissue does not contain much probably was chosen because in the first half of the 20th century, when many nutri- water. Adipose tissue contains only about 15% water, compared to tissues such as tional studies were performed, young muscle that contain about 80%. Thus, the 70-kg man with 15 kg stored triacylglyc- healthy medical and graduate students (who erol has only about 18 kg adipose tissue. Glycogen Our stores of glycogen in liver, muscle, and other cells are relatively small in quan- tity but are nevertheless important. Liver glycogen is used to maintain blood What would happen to a 70-kg glucose levels between meals. Thus, the size of this glycogen store fluctuates dur- man if the 135,000 kcal stored as ing the day; an average 70-kg man might have 200 g or more of liver glycogen after triacylglycerols in his 18 kg of adi- a meal but only 80 g after an overnight fast. Muscle glycogen supplies energy for pose tissue were stored instead as skeletal muscle contraction during exercise. At rest, the 70-kg man has approximately 150 g muscle glycogen? It would take approxi- mately 34 kg glycogen to store as many calo- of muscle glycogen.
Evaluation of surgery for Parkinson’s disease: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology buy kamagra chewable 100mg mastercard. Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson’s disease kamagra chewable 100 mg free shipping. The Deep Brain Stimulation for Parkinson’s Disease Study Group buy kamagra chewable 100mg cheap. Deep- brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease trusted kamagra chewable 100mg. Efﬁciency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa- responsive patients with Parkinson’s disease with severe motor ﬂuctuations: a 2-year follow-up review best 100 mg kamagra chewable. Opposite motor effects of pallidal stimulation in Parkinson’s disease. Inhibition of levodopa effects by internal pallidal stimulation. Analysis of choreoid hyperkinesia in the rhesus monkey. Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation. Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson’s disease. Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson’s disease: results of a randomized, blinded pilot study. Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson’s disease. Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the globus pallidus interna (GPi) for treatment of advanced Parkinson’s disease. Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson’s disease. Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson’s disease. Deep brain stimulation of the subthalamic nucleus for Parkinson’s disease: methodologic aspects and clinical criteria. Long-term follow up of subthalamic nucleus stimulation in Parkinson’s disease. Subthalamic nucleus versus globus pallidus internus. Safety and efﬁcacy of pallidal or subthalamic nucleus stimulation in advanced PD. Deep brain stimulation for the treatment of Parkinson’s disease: subthalamic nucleus versus globus pallidus internus. Long-term hardware-related complications of deep brain stimulation. Neurosurgery 2002; 50:1268–1274; discussion 1274– 1276. Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson’s disease. Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms. Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data. Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat. Responses of pallidal neurons to electrical stimulation of the subthalamic nucleus is experimental primates. Mechanisms of deep brain stimulation and future technical developments. High-frequency stimulation of the globus pallidus internalis in Parkinson’s disease: a study of seven cases. Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Pallidotomy and deep brain stimulation of the pallidum and subthalamic nucleus in advanced Parkinson’s disease.
For many 100mg kamagra chewable fast delivery, participation in sporting activities with peers is one of the formative events in a child’s development and this fact should not be ignored buy generic kamagra chewable 100 mg. Ultimately the individual or his or her parent or guardian will take a risk versus benefit decision which should be based on factual information and evidence discount 100mg kamagra chewable. In searching for the evidence one should look for evidence of significant numbers of adverse outcomes to athletes with a single kidney or testicle who participate in sport and who sustain injuries to these organs buy discount kamagra chewable 100 mg line. Clearly there is a risk for people with solitary organs playing sport cheap 100mg kamagra chewable fast delivery. The consequences of the worst case scenario of acute 117 Evidence-based Sports Medicine renal failure, infertility and the ensuing multi-system pathology which can arise following injury are patently obvious. But what is the incidence of such devastating outcomes? Or can we deduce the incidence so we can inform physicians and patients in assisting them to make their decisions? Aims The aim of this paper is to examine the incidence, mechanism and characteristics of renal and testicular trauma in sport with the aim of producing evidence-based advice on whether or not athletes with a single kidney or testicle should be allowed to participate in sport. The paper will also evaluate the potential for injury to individuals with a solitary kidney or testicle participating in sport. Methods The Ovid version of Medline from 1960 to 2001 was searched for papers relating to testicular and renal trauma. Papers were sought using the words renal trauma, kidney trauma, renal injury, kidney injury, testicle trauma, testis trauma, testicle injury, testis injury and solitary organ. These were also linked to the words sport, football and skiing. Results Incidence Renal trauma Renal trauma is sustained in approximately 10% of all abdominal injuries and blunt injury is the cause of renal trauma in 90% of cases. In sports the vast majority of renal trauma is blunt trauma. In most cases injuries can be managed conservatively with surgery usually being reserved for: • vascular (renal pedicle) injury • shattered kidney • expanding or pulsatile haematoma • shocked polytrauma patient. Major renal trauma is more often associated with penetrating trauma than with blunt trauma (40% vs 15%). One must adopt a high level of suspicion for renal injuries in patients with major blunt 118 Should you play sport with one kidney, one testis? About 9% of individuals suffering renal trauma will require surgical exploration. Of these there is on average an 11% nephrectomy rate although most nephrectomies are for haemorrhage, with 61% of nephrectomies being for renovascular injury. Injuries are usually sustained in conjunction with other major injuries which is not the typical pattern of renal trauma sustained in sport. Renal trauma during sport is more commonly sustained as isolated trauma rather than in conjunction with other major injuries. Estimates of the incidence of blunt renal trauma are given at about 6⋅2 per 100 000 of the population with motor vehicle collisions making up the majority of causes. A review of the literature reveals sparse evidence of injury to athletes participating with a solitary kidney or testicle. It is reasonable when trying to decide whether or not to participate in sport that an athlete should be informed of the prevalence of significant injury occurring to “normal” individuals participating in that sport. The incidence of congenital solitary kidney in the population is thought to be of the order of 1 in 1 000. It can be safely assumed therefore that a similar percentage of people playing sport are blinded to the fact that they have a solitary kidney. Terrell has reported the prevalence of crossed fused renal ectopia in the general population as varying between 1 in 200 to 1 in 7 500 cases. It is of interest that no case reports could be found where patients with previously undiagnosed solitary organs sustained major consequences to those organs during sport. In most cases the kidney is protected by ribs, fascia, the spine, paravertebral muscles and other structures. However, in cases where the kidney lies outside this, such as with hypertrophy or transplantation, the recommendation not to participate in sport is clearly easy to make and to justify. One must also acknowledge however that a single kidney is usually larger and heavier than a normal kidney and so its proximity to the ribs and spine may change and on occasions make it more vulnerable to trauma.
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