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TRANSITION-STATE ANALOGS are stable molecules that are designed to look more like the transition state than like the substrate or product. Transitionstate analogs usually bind to the enzyme they re designed to inhibit much more tightly (by 1000-fold or more) than the substrate does.

Also, seizures are said to occur in 25 percent of severely retarded patients, taking the form at rst of exor spasms and later of absence and grand mal attacks However, of more than 30 of PKU patients at the Fernald School, a number of which we have followed clinically, none had seizures or extrapyramidal signs The majority are blue-eyed and fair in skin and hair color, and their skin is rough and dry and subject to eczema A musty body odor (due to phenylacetic acid excretion) can often be detected Twothirds are slightly microcephalic The fundi are normal, and there is no visceral enlargement or skeletal abnormality There are individuals living in the community with asymptomatic PKU and normal intelligence Instances of PKU in which the symptoms are of adult onset are rare but of interest because of the entirely unexpected diagnosis.

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The four-chambered human heart (two upper atria, two lower ventricles) plus a double circulation (pulmonary circulation plus systemic circulation) is pretty typical of the heart and circulation found in both birds and other mammals. Being endotherms (or homeotherms) that regulate their own internal body temperature ( 12), birds and mammals have a great need for energy and oxygen to keep their body heat always at a fairly high level. A double circulation plus powerful four-chambered heart provide both the required force to pump a large volume of heated blood and a separate pulmonary circulation that adds plenty of oxygen to the blood. The pulmonary (right-heart) circulation in mammals, therefore, is specialized for adding oxygen to the bloodstream. But the systemic (left-heart) circulation specializes in extracting oxygen from the bloodstream and delivering it to the tissues of the major organ systems. In the process, carbon dioxide is picked up from the tissues. The circulation in vertebrates that are heterotherms (poikilotherms), such as sh, amphibians, and reptiles, is quite another matter. Fish have a twochambered heart with only a single circulation. Amphibians rely upon a three-chambered heart (two atria, one ventricle) beating within their chests. Reptiles, likewise, possess a three-chambered heart, with two atria and one ventricle that is partially subdivided. Both amphibians and reptiles have double circulations, but there is much less specialization of function of the two circulations.

The few such cases reported and summarized by Kassim and colleagues, with a case of their own, have developed a progressive spastic paraparesis, some with mild dementia The phenylalanine levels have been at values that re ect total or partial enzyme de ciency The nding of high levels of serum phenylalanine (above 15 mg/dL) and of phenylpyruvic acid in the blood, CSF, and urine are diagnostic of PKU The level is normal at birth and rises only after the rst few days But screening by the Guthrie (ferric chloride) test will reliably identify the patient at risk The addition of 3 to 5 drops of 10% ferric chloride to 1 mL of urine is a simple and informative test It yields an emerald-green color that reaches a peak intensity in 3 to 4 min and fades in 20 to 40 min.

In contrast, the green-brown color in the urine of patients with histidinemia is permanent In maple syrup urine disease, the ferric chloride test gives a navy-blue color; propionic and methylmalonic acidemia and either ketones or salicylates in the urine yield a purple color The fundamental biochemical abnormality is a de ciency of the hepatic enzyme PA hydroxylase; the failure of conversion of PA to tyrosine results in the excretion of phenylpyruvic acid by affected individuals The precise step that is faulty in the complex phenylalanine hydroxylating reaction is still unknown..

Name of First Tab Page (PROPERTIES_INITIAL_TAB) Behavior Allow Navigation (INTERACTION_ALLOWED) Data Binding Properties Source (PROPERTIES_SOURCE)

true to delete messages older than the number of days specified by the delete expired IMAP messages on quit after property when you quit Entourage; false to keep the messages that have passed their best-before date An integer giving the number of days after which to delete IMAP messages true to delete all expired messages from the Deleted Items folder when you quit Entourage

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