Metabolic markers degradation

Since iron is involved in many central nervous system processes that could affect infant behaviour and development, iron deficiency has adverse effects on brain development, both pre- and post-natal. In various epidemiological studies, it is reported that children with iron-deficiency anaemia have poorer performances on tests of some specific cognitive function. Animal experiments have identified some of the defects of reduced iron availability on brain function, which include post-translational changes (which result in a failure of iron incorporation into protein structures which are subsequently degraded), vulnerability of the developing hippocampus (with loss of the neuronal metabolic marker cytochrome c oxidase), and altered dendritic stmcture. Iron deficiency will also have a direct effect on myelin, including a decrease in myelin lipids and proteins, as well as neurotransmitter systems, since iron... 

Fig. 4.1. Tyrosine degradation pathway. Metabolic markers are framed. Possible metabolic disorders are marked with boxes, 4.1, fumarylacetoacetase 4.2, tyrosine aminotransferase 4.3, 4-hydroxyphenylpyruvate dioxygenase 4.5, homogentisate dioxygenase. Inhibition by succinylacetone and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-l,3-cyclo-hexanedione) are indicated by crosses. 5-ALA, 5-aminolevulinate...

In this chapter, after an overview of bone and mineral metabolism, we discuss the clinical chemistry of calcium, phosphate, and magnesium the hormones regulating these minerals the major disorders of bone and the clinical use of markers of bone formation and degradation. A goal of the chapter is to provide, in one place, a view of these highly interrelated topics. 

Hydroxyproline. from the breakdown of collagen, can be used to monitor bone resorption. However, urinary hydroxyproline is markedly inlluenced by dietary gelatin. Better markers of resorption are required. One candidate would seem to be another collagen degradation product the I ragmcnts of the molecule containing the pyridinium cross links. Deoxypyridinolinc is one such crosslink which is specific for bone, and not metabolized or influenced by diet. 

Selection of the appropriate marker residue may be challenging for some antibiotics, particularly those that typically are prepared from fermentation media and may contain multiple active constituents in variable proportions according to the particular manufacturer, such as gentamicin." For these substances, there is batch-to-batch variability, so the ratios of the components are not necessarily consistent, and therefore standards of individual components are preferable for reliable quantification. The rates at which certain components may be more readily metabolized or eliminated from tissues may differ from those of other components. As a result, the residue profile found can vary according to sample collection time since the last treatment, as well as sample storage time and temperature if particular components are subject to degradation on storage prior to analyses. 

Fig. 4.2. Increased tyrosine concentration is caused by inborn or acquired deficiency of the first two enzymes of the tyrosine degradation pathway (the increased tyrosine concentration of tyrosinemia type I is caused by secondary deficiency of 4-hydroxyphenyl-pyruvate dioxygenase). Hypertyrosinemia in the newborn is in most instances not due to inborn errors of tyrosine metabolism, but rather to liver immaturity or other unspecific liver affections. However, whenever hypertyrosinemia is found, the pathognomonic sign of tyrosinemia type I should be excluded by a sufficiently sensitive analysis of suc-cinylacetone and related metabolites. Decreased activity of porphobilinogen synthase activity in RBC is a sensitive and easily performed marker for increased concentrations of succinylacetone, which may be used as a first line diagnostic test before positive identification of succinylacetone and related metabolites by GC-MS can be achieved. It should also be noted that increased excretion of phenolic tyrosine metabolites is always found in hypertyrosinemia and is of no differential diagnostic value...

Fig. 6.1. The L-leucine degradative pathway. Reactions for which inherited metabolic disorders have not been conclusively identified include A, leucine-isoleucine aminotransferase and the majority of the 3-methylglutaconic acidurias (6.6-6.7). 6.1, Branched-chain a-ketoacid dehydrogenase (BCKD) complex, a reaction also occurring in the initial steps of L-isoleucine and L-valine degradation 6.2, isovaleryl-CoA dehydrogenase 6.3, 3-methylcrotonyl-CoA carboxylase 6.4, 3-methylglutaconyl-CoA hydra-tase 6.8, HMG-CoA lyase. Pathologic urinary metabolites used as specific markers in the differential diagnosis are presented in squares. Abbreviation Co A, coenzyme A...

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