By J. Osko. Northcentral University.
Two H C OH reactions in the pentose phosphate pathway use transketolase generic 5mg eldepryl fast delivery treatment hepatitis b; in the first, the 2-car- CH OPO2– 2 3 bon keto fragment from xylulose 5-phosphate is transferred to ribose 5-phosphate Xylulose 5–phosphate to form sedoheptulose 7-phosphate, and in the other, a 2-carbon keto fragment (usu- + ally derived from xyulose 5-phosphate) is transferred to erythrose 4-phosphate to H O form fructose 6-phosphate. C H H C OH H O H C CH OPO2– 2 3 H Ribose 5–phosphate H C OH thiamine H pyrophosphate transketolase CH OPO2– 2 3 H O Ribose 5–phosphate C isomerase H CH OPO2– 2 3 CH2OH Glyceraldehyde 3–phosphate + H CH2OH H C OH C CH OPO2– 2 3 HO Ribulose 5–phosphate H epimerase H H CH2OH CH OPO2– 2 3 Sedoheptulose 7–phosphate HO H C OH Fig. Two-carbon unit transferred by trans- CH OPO2– ketolase. Transketolase cleaves the bond next to 2 3 the keto group and transfers the 2-carbon keto Xylulose 5–phosphate fragment to an aldehyde. Thiamine pyrophos- phate carries the 2-carbon fragment, forming a Fig. Ribulose 5-phosphate is epimerized (to xyulose 5-phosphate) and isomerized (to covalent bond with the carbon of the keto group. CHAPTER 29 / PATHWAYS OF SUGAR METABOLISM: PENTOSE PHOSPHATE PATHWAY, FRUCTOSE, AND GALACTOSE METABOLISM 535 Transaldolase transfers a 3-carbon keto fragment from sedoheptulose 7-phos- The transketolase activity of red phate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6- blood cells is used to measure thi- phosphate (Fig. The aldol cleavage occurs between the two hydroxyl carbons amine nutritional status and diag- nose the presence of thiamine deficiency. This reaction is simi- The activity of transketolase is measured in lar to the aldolase reaction in glycolysis, and the enzyme uses an active amino the presence and absence of added thiamine group, from the side chain of lysine, to catalyze the reaction. If the thiamine intake of a The net result of the metabolism of 3 moles of ribulose 5-phosphate in the pen- patient is adequate, the addition of thiamine tose phosphate pathway is the formation of 2 moles of fructose 6-phosphate and pyrophosphate does not increase the activ- 1 mole of glyceraldehyde 3-phosphate, which then continue through the glycolytic ity of transketolase because it already pathway with the production of NADH, ATP, and pyruvate. Because the pentose contains bound thiamine pyrophosphate. If phosphate pathway begins with glucose 6-phosphate, and feeds back into the the patient is thiamine deficient, transketo- lase activity will be low, and adding thiamine pyrophosphate will greatly stimulate the reaction. Al Martini was diagnosed in Chap- ter 19 as having beriberi heart disease result- CH2OH ing from thiamine deficiency. The diagnosis C was based on laboratory tests confirming HO the thiamine deficiency. H H H CH OPO2– 2 3 Sedoheptulose 7–phosphate + H O C H CH OPO2– 2 3 Glyceraldehyde 3–phosphate transaldolase H O C H H CH OPO2– 2 3 Erythrose 4–phosphate + CH2OH C HO H C OH H C OH CH OPO2– 2 3 Fructose 6–phosphate Fig. Transaldolase transfers a 3-carbon fragment that contains an alcohol group next to a keto group. A balanced sequence of reactions in the pentose phosphate pathway. The interconversion of sugars in the pentose phosphate path- way results in conversion of 3 glucose 6-phosphate to 6 NADPH, 3 CO2, 2 fructose 6-phosphate, and one glyceraldehyde 3-phosphate. The reaction sequence starting from glucose-6-P, and involving both the oxidative and nonoxidative phases of the path- way, is shown in Figure 29. GENERATION OF RIBOSE 5-PHOSPHATE FROM INTERMEDIATES OF GLYCOLYSIS The reactions catalyzed by the epimerase, isomerase, transketolase, and transal- dolase are all reversible reactions under physiologic conditions. Thus, ribose 5-phosphate required for purine and pyrimidine synthesis can be generated from intermediates of the glycolytic pathway, as well as from the oxidative phase of the pentose phosphate pathway. The sequence of reactions that generate ribose 5-phos- phate from intermediates of glycolysis is indicated below. Transketolase (1) Fructose-6-P glyceraldehyde-3-P Erythrose-4-P Xyulose-5-P Transaldolase (2) Erythrose-4-P Fructose-6-P Sedoheptulose-7-P Glyceraldehyde-3-P Transketolase (3) Sedoheptulose-7-P Glyceraldehyde-3-P Ribose-5-P Xyulose-5-P Epimerase (4) 2 Xyulose-5-P 2 Ribulose-5-P Isomerase (5) 2 Ribulose-5-P 2 Ribose-5-P Net Equation : 2 Fructose-6-P Glyceraldehyde-3-P 3 Ribose-5-P CHAPTER 29 / PATHWAYS OF SUGAR METABOLISM: PENTOSE PHOSPHATE PATHWAY, FRUCTOSE, AND GALACTOSE METABOLISM 537 C. Role of the Pentose Phosphate Pathway in the Table 29. Pathways That Require NADPH Generation of NADPH In general, the oxidative phase of the pentose phosphate pathway is the major Detoxification source of NADPH in cells. NADPH provides the reducing equivalents for biosyn- • Reduction of oxidized glutathione thetic reactions and for oxidation–reduction reactions involved in protection against • Cytochrome P450 monooxygenases the toxicity of ROS (see Chapter 24). The glutathione-mediated defense against Reductive synthesis oxidative stress is common to all cell types (including the red blood cell), and the • Fatty acid synthesis requirement for NADPH to maintain levels of reduced glutathione probably • Fatty acid chain elongation accounts for the universal distribution of the pentose phosphate pathway among dif- • Cholesterol synthesis ferent types of cells. NADPH is also used for ana- • Neurotransmitter synthesis bolic pathways, such as fatty acid synthesis, cholesterol synthesis, and fatty acid • Nucleotide synthesis chain elongation (Table 29. It is the source of reducing equivalents for • Superoxide synthesis cytochrome P450 hydroxylation of aromatic compounds, steroids, alcohols, and drugs. The highest concentrations of glucose 6-phosphate dehydrogenase are found in phagocytic cells, where NADPH oxidase uses NADPH to form superoxide from molecular oxygen. The superoxide then generates hydrogen peroxide, which kills the microorganisms taken up by the phagocytic cells (see Chapter 24). The entry of glucose 6-phosphate into the pentose phosphate pathway is con- How does the net energy yield trolled by the cellular concentration of NADPH.
This holes were drilled just before to rod insertion purchase eldepryl 5 mg on line symptoms zinc toxicity, pelvic fix- case also demonstrates two major errors. One is that the ation was abandoned and he was only instrumented to L5 procedure needs to be planned for progressive increase in (Figure C9. Postoperative radiographs showed good blood loss, which the team must be prepared to address; but not complete correction of the pelvic obliquity. His that means the pelvic holes should be drilled early in the postoperative recovery was uneventful with greatly di- case when there is little blood loss. The second error is minished gastroesophageal reflux. Immediately after sur- that end-to-end rod connectors located at the same level gery, sitting was much improved. He again presented have a high failure rate and this should be avoided. We 9 months following surgery with increased sitting difficulty had three such failures until we learned this lesson. The tube can be left open to the air until the end of the case when it is placed under water seal. Bleeding Problems Intraoperative bleeding is a well-recognized problem in children with CP. This bleeding is worse than for other neuromuscular conditions and may be made even worse if children are on valproate sodium for seizure control. Another factor may involve chronic dehydration and contraction of the intravascular fluid volume, which many children have. This intravascular fluid space, if rapidly expanded under the stress of surgery, may cause acute dilution of the coagulation factors. However, this increased risk for bleeding is multi- factorial, as there has been little effect with attempts to raise specific coagu- lation factors with desmopressin acetate. Often, there are situations where children appear to be doing very well and then have a sudden decrease in the ability of clot for- mation and increased bleeding begins. Ideally, the coagulopathy can be treated before it becomes this obvious by the early administration of fresh- frozen plasma when approximately one half of the blood volume has been lost. In children on valproate sodium, phenobarbital, or other drugs known to cause increased bleeding, as well as children with severe neurologic in- volvement, earlier transfusion of fresh-frozen plasma may be considered. Periodic blood samples should be obtained, especially as one blood volume of loss is approached, to monitor platelet count. If the platelet count falls below 100,000 during surgery, platelet transfusion should be given. Hemoglobin should be maintained above 8 grams during the surgical procedure, and the goal is to maintain blood pressure at a mean of between 60 and 80 mmHg. More aggressive hypo- tensive anesthesia is not beneficial because most of the bleeding is venous in origin. Maintaining a low venous pressure is beneficial in decreasing blood loss, but this can be very dangerous. Children may go from maintaining a blood pressure of 60 mmHg, and if the intravascular volume is being main- tained low to help with bleeding, they may suddenly drop to a systolic pres- sure of less than 30 mmHg. It is better to have a little more margin of safety even if there may be a little more bleeding. Surgeons must be prepared to handle high blood loss (Case 9. The value of blood salvage in this group of children is uncertain because most of the blood loss tends to come at the end of the procedure, especially with bone decortication and facetectomy. To most adequately use blood salvage, the blood needs to be obtained through suction and there should be no wound coagulant, such as thrombin and Gelfoam, used in the wound. In our facility, there is not much difference in the amount of blood lost and the amount of donor transfusion, whether blood salvage is used or not. Also, there is debate about how much electrocautery should be used, with some surgeons doing much of the dissection with electrocautery and others using it only to con- trol points of bleeding. Sur- geons must be aware that some children with CP have high blood loss with surgery and some have very minimal blood loss. Except for children with the most severe neurologic deficit and possibly those on seizure medications, it is impossible to predict exactly which children will have high blood loss.
Some of its components are Globin chains recycled generic eldepryl 5mg without prescription medicine zetia, and the remainder leaves the body as a brown fecal pigment called stercobilin. This protein in red blood cells consists of four dietary protein and iron are still essential to maintain supplies. Box 5-2 • Health Maintenance The Cold Facts about the Common ColdThe Cold Facts about the Common Cold very year, an estimated one billion Americans suffer from temperature and humidity, these particles may live as long as Ethe symptoms of the common cold—runny nose, sneez- 3 to 6 hours, and others who touch the contaminated surface ing, coughing, and headache. Although most cases are mild may pick up the particles on their hands. More than 200 different viruses are ◗ Wash hands frequently to remove any viral particles you known to cause cold symptoms. Colds spread primarily from contact with a contaminated There are currently no medically proven cures for the com- surface. When an infected person coughs or sneezes, small mon cold, and treatments only ease the symptoms. Because droplets of water filled with viral particles are propelled viruses cause the common cold, antibiotics are of no benefit. One unshielded sneeze may spread hundreds Getting plenty of rest and drinking lots of fluids are the best of thousands of viral particles several feet. It is made of a meshwork of small, bony plates filled with red wn as os- marrow. Spongy bone is found at the epiphyses (ends) of ne, which the long bones and at the center of other bones. Figure 7- s up the 4 shows a photograph of both compact and spongy tissue of other in a bone section. What are the scientific names for the shaft and the xtend out ends of a long bone? What layer of connective tissue surrounds a fascicle of muscle fibers? The lesser der fibu trochanter, a smaller elevation, is located on the thus, it medial side. On the posterior surface there is a olus (m long central ridge, the linea aspera, which is a lower en point for attachment of hip muscles. Learning the meanings of these parts can help you remember words and interpret unfamiliar terms. WORD PART MEANING EXAMPLE Bones dia- through, between The diaphysis, or shaft, of a long bone is between the two ends, or epiphyses. Divisions of the Skeleton para- near The paranasal sinuses are near the nose. Isometric contractions—tension increases, but muscle A. In walls of hollow organs, vessels, and respiratory pas- sageways III. Involuntary; produces peristalsis; contracts and relaxes a. Tendon—cord of connective tissue that attaches slowly muscle to bone B. Cardiac muscle (1) Origin—attached to more fixed part 1. Muscle of heart wall (2) Insertion—attached to moving part 2. Involuntary; self-excitatory attaches muscle to bone or other muscle C. Cells long, cylindrical; multiple nuclei; heavily striated 2. Synergists—steady body parts and assist prime mover B. Levers and body mechanics—muscles function with skele- II. Generation of heat c Force—muscle contraction Building Understanding Fill in the blanks.
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