Phases of metabolism

Brain edema, often associated with increased intracranial pressure, may accompany the acute phase of metabolic decompensation in the aminoacidurias 671... 

Imbalances of brain amino acids may hinder the synthesis of brain lipids, leading to a diminution in the rate of myelin formation. Decreases of lipids, proteolipids and cerebrosides (Ch. 3) have been noted in several of these syndromes, e.g. maple syrup urine disease, when intra-myelinic edema is a prominent finding, particularly during the acute phase of metabolic decompensation [9]. Pathological changes in brain myelin are common, especially in infants who die early in life. The fundamental... 

Pantothenic acid is a metabolic precursor to coenzyme A, which is involved in a very large number of reactions that occur in all phases of metabolism. 

The second phase of metabolism consists of synthetic reactions that convert active compounds into inactive excretory products. Drugs that contain suitable chemical groups, such as —OH, —NHa, or —COOH, can undergo these synthetic conjugation reactions if not present in the parent compound, such drugs may be introduced during phase one reactions. Phase one and phase two metabolic reactions occur sequentially. 

Catabolism is the degradative phase of metabolism in which organic nutrient molecules (carbohydrates, fats, and proteins) are converted into smaller, simpler end products (such as lactic acid, C02, NH3). Catabolic pathways release energy, some of which is conserved in the formation of ATP and reduced electron carriers (NADH, NADPH, and FADH2) the rest is lost as heat. In anabolism, also called biosynthesis, small, simple precursors are built up into larger and more complex... 

Anabolic the phase of metabolism in which simple substances are synthesized into the complex materials of living tissue. 

Another reason for having slightly different pathways is that the corresponding anabolic and catabolic routes must be independently regulated. Otherwise, if the two phases of metabolism shared the exact pathway (only in reverse) a slowdown in the anabolic pathway would slow catabolism, and vice versa. 

Most infants are slow acetylators and may accumulate toxic levels of those drugs that are metabolized by this second phase of metabolism route. Renal perfusion and glomerular filtration rates (GFR) vary for the premature, 2-4 ml min-1 for neonates, 25 ml min-1 and by 1-1.5 years old, 125 ml min-1, which is equivalent to adult clearance rates (Arant, 1978). The potential toxic implication of renal metabolites and elimination of unchanged drug in the very young are obvious (Stewart and Hampton, 1987). 

The metabolism of xenobiotics in higher plants has been studied extensively over the last 20 years. In common plant species such as corn, it is frequently possible to predict the conjugation reactions that may be utilized in the initial phases of metabolism of a new xenobiotic. In less commonly studied species, predictions are more uncertain and exotic metabolites sire occaslonaly formed. In those cases where phase I oxidative reactions are likely, it is difficult to predict the course of metabolism because phase I oxidation reactions in plants are frequently very substrate and species specific. Phase I oxidative reactions have a profound effect on ensuing conjugation reactlcxis. The presence of multiple functional groups on a xenobiotic also Increases the uncertainty of the route of metabolism likely to be followed in a particular species. 

Compounds that serve as energy carriers for the chemotrophs, linking catabolic and biosynthetic phases of metabolism, are adenosine phosphate and reduced pyridine nucleotides (such as nicotinamide dinucleotide or NAD). The structure of adenosine triphosphate (ATP) is shown in Fig. 1. It contains two energy-rich bonds, which upon hydrolysis, yield nearly eight kcal/mole for each bond broken. ATP is thus reduced to the diphosphate (ADP) or the monophosphate (AMP) form. 

In addition to the regulatory mechanisms described above, metabolism is further regulated by compartmentalization. For example, the anaerobic phase of metabolism takes place in the cytosol, and the aerobic or respiratory phase occurs in the mitochondria. 

After these substances are transported to the cells, anabolic reactions, the second main type of reaction, occur. In this phase of metabolism. 

FIGURE 2.16 Illustration of the kinetic phase of metabolism for toxicants and protoxicants. In this phase, a protoxicant may be metabolically converted to a toxic species. A toxicant may be detoxified and excreted without doing harm, remain unchanged as an active parent compound that may have a toxic effect, or converted to another active metabolite that is potentially toxic. 

---