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Malonyl CoA NADPH provides the reducing equivalents for these reactions generic toprol xl 50 mg online. Phosphopantetheinyl residue of the original acetyl group is elongated by two carbons 50mg toprol xl with mastercard. The portion The 4-carbon fatty acyl chain is then transferred to the cysteinyl sulfhydryl group derived from the vitamin trusted toprol xl 100 mg, pantothenic acid, is and subsequently condenses with a malonyl group. Phosphopantetheine is covalently repeated until the chain is 16 carbons in length. At this point, hydrolysis occurs, and linked to a serine residue of the acyl carrier palmitate is released (Fig. The Palmitate is elongated and desaturated to produce a series of fatty acids. In the sulfhydryl group reacts with malonyl CoA to liver, palmitate and other newly synthesized fatty acids are converted to triacyl- form a thioester. Addition of a 2-carbon unit to an acetyl group on fatty acid synthase. The mal- P onyl group attaches to the phosphopantetheinyl residue (P) of the ACP of the fatty acid syn- thase. The acetyl group, which is attached to a cysteinyl sulfhydryl group, condenses with the S SH malonyl group. The carbon that eventu- C O ally forms the -methyl group of palmitate is labeled. CH2 CH2 In the liver, the oxidation of newly synthesized fatty acids back to acetyl CoA via ωCH 3 the mitochondrial -oxidation pathway is prevented by malonyl CoA. Carnitine:palmitoyltransferase I, the enzyme involved in the transport of long-chain Fig. Reduction of a -ketoacyl group fatty acids into mitochondria (see Chapter 23), is inhibited by malonyl CoA (Fig. Malonyl CoA levels are elevated when acetyl CoA carboxylase is activated, and, thus, fatty acid oxidation is inhibited while fatty acid synthesis is proceeding. This inhibition prevents the occurrence of a futile cycle. Elongation of Fatty Acids the first acetyl CoA that binds to fatty acid synthase appear in After synthesis on the fatty acid synthase complex, palmitate is activated, forming palmitate, the final product? Palmityl CoA and other activated long-chain fatty acids can be CHAPTER 33 / SYNTHESIS OF FATTY ACIDS, TRIACYLGLYCEROLS, AND THE MAJOR MEMBRANE LIPIDS 601 FA 1 2 synthase NADPH + H+ P P P P P CO2 SH SH S SH SH S S S S S NADP+ H C O C O C O C O C O 3 ωCH ωCH CH ωCH CH 3 3 2 3 2 – O COO C O ωCH P CH C SCoA 3 3 S SH Acetyl CoA CO ATP ADP + Pi O 2 C O CH2 C SCoA Biotin CH2 – acetyl CoA carboxylase COO HCOH Malonyl CoA ω CH3 Palmitate (C16) 4 H2O NADP+ NADPH 2NADP+ 2NADPH CO2 + H+ P P P P P P 5 4 3 2 1 5 S SH H2O S SH S S SH S S SH S S H C O C O C O C O C O C O C O CH2 CH2 CH2 CH2 CH2 CH2 CH CH C O COO– CH CH CH CH 2 2 2 2 CH CH ωCH ωCH ωCH ωCH 2 2 3 3 3 3 CH2 CH2 ωCH ωCH 3 3 Fig. Synthesis of palmitate on the fatty acid synthase complex. Malonyl CoA provides the 2-carbon units that are added to the growing fatty acyl chain. The addition and reduction steps are repeated until palmitate is produced. Transfer of the malonyl group to the phosphopantetheinyl residue. P a phosphopantetheinyl group attached to the fatty acid synthase complex; Cys-SH a cysteinyl residue. Malonyl CoA serves as the donor of the 2-carbon units, and NADPH provides the reducing equivalents. The series of elongation reac- tions resemble those of fatty acid synthesis except that the fatty acyl chain is attached to coenzyme A rather than to the phosphopantetheinyl residue of an ACP. The major elongation reaction that occurs in the body involves the conversion of palmityl CoA (C16) to stearyl CoA (C18). Very-long-chain fatty acids (C22 to C24) are also produced, particularly in the brain. Desaturation of Fatty Acids Desaturation of fatty acids involves a process that requires molecular oxygen (O2), The methyl group of acetyl CoA NADH, and cytochrome b5.

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The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease buy toprol xl 50 mg on line. Research diagnostic criteria for Parkinson’s disease cheap 50 mg toprol xl mastercard. In: Streifler M cheap toprol xl 50mg with amex, Korczyn A, Melamed E, Youdim M, eds. Advances in Neurology: Parkinson’s Disease: Anatomy, Pathology, and Therapy. Accuracy of clinical diagnosis in parkinsonism prospective study. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. In his 1817 ‘‘An Essay on the Shaking Palsy,’’ James Parkinson recorded many features of the condition that now bears his name (1). Parkinson emphasized the tremor at rest, flexed posture, festinating gait (Fig. Charcot and others later pointed out that the term paralysis agitans used by Parkinson was inappropriate, because in Parkinson’s disease (PD) the strength was usually well preserved and many patients with Parkinson’s disease did not shake. Although traditionally regarded as a motor system disorder, PD is now considered to be a much more complex syndrome involving the motor as well as the nonmotor systems. For example, oily skin, seborrhea, pedal edema, fatigability, and weight loss are recognized as nonspecific but nevertheless typical parkinsonian features. The autonomic involvement is responsible for orthostatic hypotension, paroxysmal flushing, diaphoresis, problems with thermal regulation, constipation, and bladder, sphincter, and sexual disturbances. The involvement of the thalamus and the spinal Copyright 2003 by Marcel Dekker, Inc. The special sensory organs may also be involved in PD and cause visual, olfactory, and vestibular dysfunction (3). A large number of studies have drawn attention to the protean neurobehavioral abnormalities in PD, such as apathy, fearfulness, anxiety, emotional lability, social withdrawal, increasing dependency, depression, dementia, bradyphrenia, a type of anomia termed the ‘‘tip-of-the-tongue phenomenon,’’ visual-spatial impairment, sleep disturbance, psychosis, and other psychiatric problems (4,5). The rich and variable expression of PD often causes diagnostic confusion and a delay in treatment. In the early stages, parkinsonian symptoms are often mistaken for simple arthritis or bursitis, depression, normal aging, Alzheimer’s disease, or stroke (Fig. PD often begins on one side of the body, but usually becomes bilateral within a few months or years. However, parkinsonism may remain unilateral, particularly when it is a late sequela of posttraumatic hemiatrophy or when it is due to a structural lesion in the basal ganglia (6). In a survey of 181 treated PD patients, Bulpitt Copyright 2003 by Marcel Dekker, Inc. However, only 9 of these symptoms were reported by the patients, with more than fivefold excess compared with those of a control population of patients randomly selected from a general practice. These common symptoms included being frozen or rooted to a spot, grimacing, jerking of the arms and legs, shaking hands, clumsy hands, salivation, poor concentration, severe apprehension, and hallucinations. However, even these frequent symptoms are relatively nonspecific and do not clearly differentiate PD patients from diseased controls. In many cases, a follow-up for several years is needed before the diagnosis becomes apparent. During this period PD patients, compared to normal controls, had a higher frequency of mood disorder, ‘‘fibromyalgia,’’ and shoulder pain.

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As the head moves cheap 25 mg toprol xl amex, the thick fluid above the receptor cells order toprol xl 25mg free shipping, weighted with otoliths buy 50mg toprol xl, pulls on the cilia of the cells, generating a nerve impulse. ZOOMING IN ✦ What happens to the cilia on the receptor cells when the fluid around them moves? Box 11-2 • Health Professions AudiologistsAudiologists udiologists specialize in preventing, diagnosing, and treat- levels and teach the public how to prevent hearing loss. To per- Aing hearing disorders caused by injury, infection, birth de- form these duties, audiologists need a thorough understanding fects, noise, or aging. They diagnose hearing disorders by tak- of anatomy and physiology. Audiologists design and implement or university and must pass a national licensing exam. Job prospects are cochlear implants and educating them about their use, or good, as the need for audiologists’ specialized skills will in- teaching alternate communication skills, such as lip reading. For more informa- Audiologists also measure workplace and community noise tion, contact the American Academy of Audiology. THE SENSORY SYSTEM ✦ 237 ◗ Other Special Sense Organs The sense organs of taste and smell are designed to respond to chemical stimuli. Sense of Taste The sense of taste, or gustation (gus- TA-shun), involves receptors in the tongue and two different nerves that carry taste impulses to the brain (Fig. The taste receptors, known as taste buds, are located along the edges of small, depressed areas called fis- sures. Taste buds are stimulated only if the substance to be tasted is in solu- tion or dissolves in the fluids of the mouth. Receptors for four basic tastes are localized in different regions, 11 forming a “taste map” of the tongue (see Fig. As the body spins or moves in different directions, the cilia bend as the head changes posi- terior part of the tongue. Taste maps vary among people, but in each person certain regions of the tongue are more sen- sitive to a specific basic taste. Other tastes are a combina- the vestibulocochlear nerve, or the brain areas concerned tion of these four with additional smell sensations. It may result from prolonged exposure to recently, researchers have identified some other tastes be- loud noises, from the use of certain drugs for long peri- sides these basic four: water, alkaline (basic), and metal- ods, or from exposure to various infections and toxins. Another is umami (u-MOM-e), a pungent or savory People with severe hearing loss that originates in the taste based on a response to the amino acid glutamate. This pros- Glutamate is found in MSG (monosodium glutamate), a thetic device stimulates the cochlear nerve directly, by- flavor enhancer used in Asian food. Water taste receptors passing the receptor cells, and may restore hearing for are mainly in the throat and may help to regulate water medium to loud sounds. Presbycusis (pres-be-KU-sis) is a slowly progressive The nerves of taste include the facial and the glos- hearing loss that often accompanies aging. The condition sopharyngeal cranial nerves (VII and IX). The interpreta- involves gradual atrophy of the sensory receptors and tion of taste impulses is probably accomplished by the cochlear nerve fibers. The affected person may experience lower frontal cortex of the brain, although there may be a sense of isolation and depression, and psychological no sharply separate gustatory center. Because the ability to hear high- pitched sounds is usually lost first, it is important to ad- Sense of Smell dress elderly people in clear, low-pitched tones. Box 11-2 offers information on how audiologists help to treat hear- The importance of the sense of smell, or olfaction (ol- ing disorders. This sense helps to 238 ✦ CHAPTER ELEVEN factory center in the brain’s temporal cortex. The interpretation of smell is closely related to the sense of taste, but a greater variety of dissolved chemicals can be detected by smell than by taste.

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