Metabolism disorders

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

A much more common metabolic disorder, lactose intolerance, occurs commonly in most parts of the world (notable exceptions being some parts of Africa and northern Europe). Lactose intolerance is an inability to digest lactose because of the absence of the enzyme lactase in the intestines of adults. The symptoms of this disorder, which include diarrhea and general discomfort, can be relieved by eliminating milk from the diet. 

The a-oxidation pathway is defective in Refsum s disease, an inherited metabolic disorder that results in defective night vision, tremors, and other neurologic abnormalities. These symptoms are caused by accumulation of phytanic acid in the body. Treatment of Refsum s disease requires a diet free of chloro-... 

About 4.5 million Americans have heart failure (HF). It is the most frequent cause of hospitalization for individuals older than 65 years. Some patients, with treatment, may lead nearly normal lives, whereas more than 50% of individuals with severe HF die each year. HF is a complex clinical syndrome that can result from any number of cardiac or metabolic disorders such as ischemic heart disease, hypertension, or hyperthyroidism. Any condition that impairs the ability of the ventricle to pump blood can lead to HF In HF, die heart... 

Poulton, J., Land, J. (1990), The genetics of metabolic disorders of muscle. In Muscle Metabolism (Harris, J.B., Turnbull, D.M., eds.), pp. 621-664, Balliere-Tindall, London. 

While ammonia, derived mainly from the a-amino nitrogen of amino acids, is highly toxic, tissues convert ammonia to the amide nitrogen of nontoxic glutamine. Subsequent deamination of glutamine in the liver releases ammonia, which is then converted to nontoxic urea. If liver function is compromised, as in cirrhosis or hepatitis, elevated blood ammonia levels generate clinical signs and symptoms. Rare metabolic disorders involve each of the five urea cycle enzymes. 

METABOLIC DISORDERS ARE ASSOCIATED WITH EACH REACTION OF THE UREA CYCLE... 

Metabolic disorders of urea biosynthesis, while extremely rare, illustrate four important principles (1) Defects in any of several enzymes of a metabolic pathway enzyme can result in similar clinical signs and symptoms. (2) The identification of intermediates and of ancillary products that accumulate prior to a metabolic block provides insight into the reaction that is impaired. (3) Precise diagnosis requires quantitative assay of the activity of the enzyme thought to be defective. (4) Rational therapy must be based on an understanding of the underlying biochemical reactions in normal and impaired individuals. 

METABOLIC DISORDERS OF BRANCHED-CHAIN AMINO ACID CATABOLISM... 

Metabolic disorders of phenylalanine catabolism include phenylketonuria (PKU) and several hyper-phenylalaninemias. 

The catabolism of leucine, valine, and isoleucine presents many analogies to fatty acid catabolism. Metabolic disorders of branched-chain amino acid catabolism include hypervalinemia, maple syrup urine disease, intermittent branched-chain ketonuria, isovaleric acidemia, and methylmalonic aciduria. 

Sequences of various bacterial genomes and other information.) Karolinska Institute Nutritional and Metabolic Diseases http // www.mic.ki.se/Diseases/cl8.html (Access to information on many nutritional and metabolic disorders.)... 

Nadler, H. L. and Egan, T. J. "Deficiency of Lysosomal Acid Phosphatase a New Familial Metabolic Disorder". 

Diabetes is a metabolic disorder where glucose metabolism in the body is impaired. Type 1 diabetes is an early onset disease in which the pancreatic cells lose the function of insulin secretion either by genetic disposition or by a viral attack. Type 2 diabetes is a late onset disease developed due to insufficient insulin secretion or insulin resistance resulting in impaired glucose metabolism. 

Studies of a network of metabolic pathways and their disorders. A metabolic disorder occurs when there is a blockage in one of the pathways because the enzyme required to catalyze the reaction is malfunctioning or missing. This results in an accumulation of metabolites on one side of the block and a dehciency of essential chemicals on the other. In many metabolic disorders, early diagnosis may prevent permanent functional damage or death. 

Investigation of the differences in crystal packing between (431) and (426) from comparison of their respective X-ray structures, revealed that (431) was more tightly packed than (442), reflected in their respective melting points of 235 and 170 °C. It was postulated that the absence of in vivo activity for (431) may be explained by the resultant reduction in water solubility and dissolution rate compared with (426). The comparatively high calculated polar surface area of (431) (122.5A ) compared with (426) (89.3 A ) was also proposed as a factor influencing the marked difference in bioavailability between the two related compounds. Compound (426) (SLV-319) is currently being developed with Bristol-Myers Squibb for the potential treatment of obesity and other metabolic disorders. Phase I trials for obesity were started in April 2004. Earlier Phase I clinical trials for the treatment of schizophrenia and psychosis, which commenced in April 2002, appear to have been abandoned. 

Because C02 is a volatile acid, it can rapidly be changed by the respiratory system. If a respiratory acid-base disturbance is present for minutes to hours it is considered an acute disorder while if it is present for days or longer it is considered a chronic disorder. By definition, the metabolic machinery that regulates HC03 results in slow changes in serum bicarbonate and all metabolic disorders are chronic. This means that there are six simple acid-base disorders as outlined in Table 25-1.2... 

Changes that follow the primary disorder and attempt to restore the blood pH to normal are referred to as compensatory changes. It should be stressed that compensation never normalizes the pH. Because all metabolic acid-base disorders are chronic and the normal respiratory system can quickly alter the PaC02, essentially all metabolic disorders are accompanied by some degree of respiratory compensation.3 Similarly, chronic respiratory acid-base disorders are typically accompanied by attempts at metabolic compensation.4,5 However, with acute respiratory acid-base disorders there is insufficient time for the metabolic pathways to compensate significantly.6 As such, acute respiratory derangements are essentially uncompensated. 

O Diabetes mellitus (DM) describes a group of chronic metabolic disorders that are characterized by hyperglycemia and are associated with long-term microvascular, macrovascular, and neuropathic complications. 

Congenital, familial, and metabolic disorders (e.g., congenital obstructive uropathy, Fabry s disease, medullary cystic disease, and nephrolithiasis)... 

Metabolic disorder (hemochromatosis, ochronosis, Wilson s disease, chondrocalcinosis, Paget s disease)... 

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