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Thus discount cipro 500mg amex, a value of approxi- Riboflavin 2H 2 e S riboflavin-H 0 purchase 1000mg cipro with visa. CALORIC VALUES OF FUELS by decreasing his intake of fat and alcohol (ethanol) cipro 500mg for sale, and increasing The caloric value of a food is directly related to its oxidation state cipro 750mg low price, which is a meas- ure of G0 for transfer of electrons from that fuel to O. The electrons donated by his content of carbohydrates. Compare the 2 structure of ethanol with that of glucose and the fuel are from its C-H and C-C bonds. On the basis of their oxi- (CH3(CH2)14COOH) have a caloric value of roughly 9 kcal/g. Glucose is already dation state, which compound provides the partially oxidized and has a caloric value of only about 4 kcal/g. O The caloric value of a food is applicable in humans only if our cells have HOH2C (HC OH)4 enzymes that can oxidize that fuel by transferring electrons from the fuel to NAD , NADP , or FAD. When we burn wood in a fireplace, electrons are trans- Glucose ferred from cellulose and other carbohydrates to O2, releasing energy as heat. However, wood has no caloric content for humans; we cannot digest it and con- CH3CH2OH vert cellulose to a form that can be oxidized by our enzymes. Cholesterol, Ethanol although a lipid, also has no caloric value for us because we cannot oxidize the O carbons in its complex ring structure in reactions that generate NADH, CH3 (CH2)16 FAD(2H), or NADPH. NADPH in Oxidation-Reduction Reactions NADP is similar to NAD and has the same reduction potential. However, NADP has an extra phosphate group on the ribose, which affects its enzyme binding (see Fig. Consequently, most enzymes use either NAD or NADP , but seldom Glucose 2 ADP, Pi both. In certain reactions, fuels are oxidized by transfer of electrons to NADP to ~P intermediates form NADPH. For example, glucose 6-P dehydrogenase, in the pentose phosphate pathway, transfers electrons from glucose 6-P to NADP instead of NAD. Consequently, the Pyruvate Lactate energy in its reduction potential is usually used in energy-requiring reactions with- out first being converted to ATP currency. Anaerobic Glycolysis is transferred from high-energy intermediates of the pathway to ADP. Because NADH from Not all ATP is generated by fuel oxidation. In anaerobic glycolysis, glucose is the pathway is reoxidized by reduction of degraded in reactions that form high-energy phosphorylated intermediates of the pyruvate to lactate, no oxygen is required. These activated high-energy intermediates provide the energy for the generation of ATP from ADP without involving electron transfer to O2. Therefore, this pathway is called anaerobic glycolysis, and ATP is generated from substrate level phosphorylation rather than oxidative phosphorylation (see Chapter Oxidases 22). Anaerobic glycolysis is a critical source of ATP for cells that have a decreased O + 4e–, 4H+ 2H O 2 2 O2 supply, either because they are physiologically designed that way (e. OXYGENASES AND OXIDASES NOT INVOLVED IN 2 ATP GENERATION H2O + Electron + S OH donor–X Approximately 90 to 95% of the oxygen we consume is used by the terminal oxi- dase in the electron transport chain for ATP generation via oxidative phosphoryla- Dioxygenases tion. The remainder of the O2 is used directly by oxygenases and other oxidases, enzymes that oxidize a compound in the body by transferring electrons directly to S + O2 SO2 O2 (Fig. The large positive reduction potential of O2 makes all of these reac- Fig. The tions extremely favorable thermodynamically, but the electronic structure of O2 fate of O2 is shown in blue. S represents an slows the speed of electron transfer. These enzymes, therefore, contain a metal ion organic substrate. CHAPTER 19 / CELLULAR BIOENERGETICS: ATP AND O2 355 A. Oxidases In palmitate and other fatty acids, most carbons are more reduced Oxidases transfer electrons from the substrate to O2, which is reduced to water than those in glucose or ethanol (H2O) or to hydrogen peroxide (H2O2).

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For example cipro 500 mg on-line, teachers have to routinely make realistic assessments concerning the functional abil- ity of a child to learn specific material best 1000mg cipro. Normal children have a widely vari- able ability to learn a level of mathematics at each age level buy 1000mg cipro, and teachers have to be aware of the level of the individual child purchase cipro 750 mg without a prescription. Some children in fourth grade may still be struggling to learn addition, while others are ready to learn geometry, but none would be ready to do calculus. In a community popula- tion of children, many will never be able to develop enough math skills to learn advanced calculus. Using this same analogy, the physical therapist needs to have a good ability to understand what the possibilities are for each individual child, while at the same time continuing to motivate the child to improve his motor skills. Understanding the child’s functional possibilities means the therapist can avoid frustrating them with unreasonable demands and help their parents understand reasonable functional goals for the child. The strategy for physical therapy is very dependent on age and functional ability. Added to the age appropriateness, the therapy plan should have specific objective, quantifiable short-term goals. Such goals include improv- ing how long the child can stand on one leg, learning to jump, using a walker independently, or improving a specific amount on a global measure such as the Gross Motor Function Measure (GMFM). These specific short-term goals can help the therapist, child, and parents judge progress. Also, this type of goal setting is an important part in the reimbursement of therapy services 160 Cerebral Palsy Management from insurance companies. Another part of the treatment plan includes teach- ing the family how to handle the child, teaching the child and family an ex- ercise program, assessing the general function of the family in the home environment, and helping the family understand the long-term expectations of the child. A difficult aspect of the therapist’s treatment plan is integrating the child’s other medical treatments with fragmented medical care. The time constraint, which does not give the therapist time to attend medical ap- pointments, leaves many therapists to gather this information from parents. Obtaining medical notes from physician visits can be another mechanism for the therapist to stay informed. The treatment program at this age, which is carried out by either a physical or occupational therapist, usu- ally includes a combination of stimulation through handling the children, sensory stimulation through positional changes, and getting the children into correct seating. Many of the techniques used in infant stimulation ap- proaches are combinations of NDT, sensory motor, and sensory integration approaches. Therapy frequency at this age may be two or three times a week; however, care should be taken not to place too high a burden on new par- ents with many medical visits. We have seen one very frustrated mother who was scheduled to see 21 medical practitioners for an 18-month-old child who had been discharged from an intensive care unit (Table 5. This num- ber is far too much of a burden, and the therapists are in a good position to sense this and help parents decide what is reasonable. This is especially help- ful when there are frequent team-generated treatment plans saying, for ex- ample, that a child should have four physical therapy treatment sessions in a week; however, due to the therapists’ schedules, he will be scheduled to see three different therapists in 1 week. This is the worst kind of fragmented care, and it is very frustrating to parents. To parents and children, therapy is an intimate relationship and there is little benefit when it is scheduled based on whoever can be found to do therapy that day. Many of these par- ents will become very confused after hearing slightly different assessments from each therapist, often with different words to describe the same concern. This scenario is to be avoided; it is far better to have fewer sessions with a consistent therapist. The efficacy of early childhood therapy has not been well documented objectively, with most studies showing no or marginal measurable benefit. This time continues to be crucial in the parents’ coming to under- stand their children’s disabilities as the impairments are slowly becoming more apparent. A close, consistent relationship with a single therapist is es- pecially beneficial during this time. This is the period where setting concrete short-term goals works well because of the children’s rapid maturation, and this is also when much of children’s play and free exploration time is motor based if they have sufficient motor ability for self movement. There are many developing adaptive equipment needs that also have to be assessed, fitted, and ordered for the children during this phase.

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As the result of a weak cough reflex buy 1000 mg cipro with visa, he is unable to clear his normal respiratory secretions and has had recurrent respiratory infections order cipro 1000 mg with visa. INTERCONVERSIONS INVOLVING UDP NUCLEOTIDE-SUGARS CH2OH Activated sugars attached to nucleotides are converted to other sugars cipro 1000 mg lowest price, oxidized to O O sugar acids buy 500mg cipro visa, and joined to proteins, lipids, or other sugars through glycosidic NH bonds. Reactions of UDP-Glucose Glycosylated UDP-glucose is an activated sugar nucleotide that is a precursor of glycogen and protein lactose, UDP-glucuronate and glucuronides, and the carbohydrate chains in proteo- glycans, glycoproteins, and glycolipids (Fig. These enzymes cosaminoglycans are discussed further in Chapter 49. In the synthesis of many of transfer sugars from nucleotide sugars to nucle- ophilic amino acid residues on proteins, such as the carbohydrate portions of these compounds, a sugar is transferred from the the hydroxyl group of serine or the amide group nucleotide sugar to an alcohol or other nucleophilic group to form a glycosidic bond of asparagine. The use of UDP as a leaving group in this reaction provides the energy cific sugars from a nucleotide sugar to a for formation of the new bond. The enzymes that form glycosidic bonds are sugar hydroxyl group of other sugars. The bond transferases (for example, glycogen synthase is a glucosyltransferase). Transferases formed between the anomeric carbon of the are also involved in the formation of the glycosidic bonds in bilirubin glucuronides, sugar and the nucleophilic group of another proteoglycans, and lactose. UDP-glucuronate is formed from UDP- 2NAD+ glucose (shown in black). Glucuronate from UDP-glucuronate is incorporated into gly- UDP–glucose cosaminoglycans, where certain of the glucuronate residues are converted to iduronate (see dehydrogenase Chapter 49). UDP-glucuronate is a precursor of UDP-xylose, another sugar residue incorpo- 2NADH + 2H+ rated into glycosaminoglycans. Glucuronate is also transferred to the carboxyl groups of bilirubin or the alcohol groups of steroids, drugs, and xenobiotics to form glucuronides. The O “ide” in the name glucuronide denotes that these compounds are glycosides. Xenobiotics are – C O pharmacologically, endocrinologically, or toxicologically active substances not endoge- O nously produced and therefore foreign to an organism. UDP-Glucuronate: A Source of Negative Charges OH UDP–Glucuronate One of the major routes of UDP-glucose metabolism is the formation of UDP- glucuronate, which serves as a precursor of other sugars and of glucuronides UDP–glucuronate ROH transferase (Fig. Glucuronate is formed by the oxidation of the alcohol on C6 of glucose (microsomal) (xenobiotics, drugs or to an acid (through two oxidation states) by an NAD -dependent dehydrogenase other OH) (Fig. Glucuronate is also present in the diet and can be formed from the O – degradation of inositol (the sugar alcohol that forms inositol trisphosphate (IP3), an C O intracellular second messenger for many hormones). Formation of Glucuronides HO The function of glucuronate in the excretion of bilirubin, drugs, xenobiotics, and OH other compounds containing a hydroxyl group is to add negative charges and Glucuronide increase their solubility. Bilirubin is a degradation product of heme that is formed in the reticuloendothelial system and is only slightly soluble in plasma. It is transported Bile or urine to the liver bound to albumin. In the liver, glucuronate residues are transferred from Fig. Formation of glucuronate and glu- UDP-glucuronate to two carboxyl groups on bilirubin, sequentially forming biliru- curonides. A glycosidic bond is formed bin monoglucuronide and bilirubin diglucuronide, the “conjugated” forms of biliru- between the anomeric hydroxyl of glucuronate bin (Fig. The more soluble bilirubin diglucuronide (as compared with uncon- and the hydroxyl group of a nonpolar com- jugated bilirubin) is then actively transported into the bile for excretion. The negatively charged carboxyl group Many xenobiotics, drugs, steroids, and other compounds with hydroxyl groups of the glucuronate increases the water solubil- and a low solubility in water are converted to glucuronides in a similar fashion by ity and allows otherwise nonpolar compounds glucuronyltransferases present in the endoplasmic reticulum and cytoplasm of the to be excreted in the urine or bile. This is one of the major conjugation pathways for High concentrations of galactose 1- excretion of these compounds.

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The slow- twitch fibers buy 750mg cipro, or type I fibers (also called slow-oxidative) generic cipro 750 mg, contain large amounts of mitochondria and myoglobin (giving them a red color) purchase 750 mg cipro with amex, utilize respiration and oxidative phosphorylation for energy buy cipro 750mg free shipping, and are relatively resistant to fatigue. Com- pared with fast-twitch fibers, their glycogen content is low. The slow-twitch fibers develop force slowly but maintain contractions longer than fast-twitch muscle. The fast-twitch fibers, or type II, can be subdivided as type IIa or IIb. Type IIb fibers (also called fast-glycolytic) have few mitochondria and low levels of myo- globin (hence, they appear white). They are rich in glycogen and use glycogenoly- sis and glycolysis as their primary energy source. These muscles are prone to fatigue, because a continued reliance on glycolysis to produce ATP leads to an increase in lactic acid levels, resulting in a drop in the intracellular pH. As the pH drops, the ability of the muscle to produce ATP also diminishes. However, fast- twitch muscle can develop greater forces than slow-twitch muscle, such that con- tractions occur more rapidly. Type IIa fibers (also called fast-oxidative glycolytic) have properties of both type I and IIb fibers and thus display functional character- istics of both fiber types. The properties of types I, IIa, and IIb fibers are summa- rized in Table 47. Muscles are a mixture of the different fiber types, but depending on the function a muscle could have a preponderance of one fiber type over another. Type I fibers are found in postural muscles such as the psoas in the back musculature or the soleus in the leg. The percentage of type I to type II will vary with the muscle. Type II fibers are more prevalent in the large muscles of the limbs that are responsible for sudden, powerful movements. Extraoc- ular muscles would also have more of these fibers than type I. Smooth Muscle Cells Smooth muscle cells are found in the digestive system, blood vessels, bladder, air- ways, and uterus. The cells have a spindle shape with a central nucleus (see Fig. The designation of smooth refers to the fact that these cells, which contain a single nucleus, display no striations under the microscope. The contraction of smooth muscle is controlled involuntarily (the cells contract and relax without any conscious attempt to have them do so; examples of smooth muscle activity include moving food Table 47. Properties of Muscle Fiber Types Type I Fibers Type II Fibers Type IIa Type IIb • Slow-twitch (slow speed • Intermediate-twitch (fast • Fast-twitch (fast speed of of contraction) speed of contraction) contraction) • Slow-oxidative (low glyco- • Fast-oxidative glycolytic • Fast-glycolytic (high glyco- gen content) fibers (intermediate gen content) glycogen levels) • High myoglobin content • Intermediate fiber • Low myoglobin content (appear red) diameter (appear white) • Small fiber diameter • High myoglobin content • Low mitochondrial (appear red) content • Increased concentration • Increased oxidative • Limited aerobic of capillaries surrounding capacity on training metabolism muscle (greater oxygen • Intermediate resistance to • Large fiber diameter delivery) fatigue • High capacity for aerobic • More sensitive to fatigue metabolism as compared with other fiber types • High resistance to fatigue • Least efficient use of energy, primarily glycolytic • Used for prolonged, • Used for sprinting and aerobic exercise resistance tasks CHAPTER 47 / METABOLISM OF MUSCLE AT REST AND DURING EXERCISE 865 along the digestive tract, altering the diameter of the blood vessels, and expelling urine A reduced flow of oxygen-rich from the bladder). In contrast to skeletal muscle, these cells have the ability to main- blood to the heart muscle may lead tain tension for extended periods, and do so efficiently, with a low use of energy. The amount of ATP that can be gen- erated by glycolysis alone is not sufficient to C. Cardiac Muscle Cells meet the energy requirements of the con- The cardiac cells are similar to skeletal muscle in that they are striated (contain fibers), tracting heart. The multicellular contacts allow the cells to act as a common unit and to con- tract and relax synchronously. Cardiac muscle cells are designed for endurance and consistency. They depend on aerobic metabolism for their energy needs because they contain many mitochondria and very little glycogen. These cells thus generate only a small amount of their energy from glycolysis using glucose derived from glycogen. NEURONAL SIGNALS TO MUSCLE For an extensive review of how muscle contracts or a detailed view of the signaling to allow muscle contraction, consult a medical physiology book. The ryanodine receptors are cal- The nerve–muscle cell junction is called the neuromuscular junction (Fig. This binding stim- coplasmic reticulum of muscle cells.

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