Metabolism of Some Individual Amino Acids

N-carbamoylglutamate, activates CPSI, does not share the undesirable properties of NAG, and has been effective in management of this deficiency. 

Arginine participates in a number of metabolic pathways depending on the cell type. It is synthesized as an inter- 

---

SECTION 17.3 Metabolism of Some Individual Amino Acids... 

Occasionally, individuals are born with very specific disorders related to the metabolism of protein or amino acids. These are often referred to as inborn errors of metabolism. Albinism, maple syrup urine disease, and phenylketonuria are examples of some of the more familiar types. 

As noted, vitamin C is needed for the production of collagen in the body, but it is also essential in the production of certain hormones such as dopamine and adrenaline. Ascorbic acid is also essential in the metabolism of some amino acids. It helps protect cells from free radical damage, helps iron absorption, and is essential for many metabolic processes. The dietary need of vitamin C is not clearly established, but the U.S. National Academy of Science has established a recommended dietary allowance (RDA) of 60 mg per day. Some groups and individuals, notably Linus Pauling in the 1980s, recommend dosages as high as... 

Some inborn errors of metabolism can be characterized by excessive urinary excretion of aromatic acid metabolites. These acids are distinct from the vanillyl acids discussed in a previous section. Phenylketonuria, alkaptonuria, and tyrosinosis can be diagnosed by determination of the aromatic acid metabolites. Aromatic acid profiles are characteristic of specific metabolic defects, and can be used to confirm diagnoses obtained from amino acid and other studies. Quantification of the individual aromatic acid gives information as to the fate of ingested amino acid in diseases such as phenylketonuria, where there is a block in the metabolic pathway involving the particular amino acid. 

It is clearly not possible to discuss here at any length, the metabolism of individual amino acids. In addition, the details of the biosynthesis and catabolism of amino acids, well reviewed in Volume II of Meister s recent book , are concerned more with the formation and breakdown of the carbon skeleton than with the introduction or loss of the amino group. Modifications of some of the twenty amino cicids normally found in proteins have been detected in some protein hydrolysates, e.g. iodinated tyrosine, phosphoserine and hydroxylysine. In some cases the modification appears to be made before the amino acid is incorporated into protein (e.g. iodination of tyrosine) while in other cases modification is believed to occur when the amino acid is already present in proteins (e.g. hydroxylation of lysine, and in some cases, of... 

Numerous studies have been published on the in vivo metabolism of peptides. However, these studies are concerned mainly with assessment of pharmacokinetic parameters such as half-life and clearance. Only seldom is the in vivo biotransformation of peptides that contain only common amino acids investigated in any detail, due to the difficulty of monitoring products of proteolysis that are identical to endogenous peptides and amino acids. More importantly, such studies fail to yield mechanistic and biochemical insights. For this reason, we begin here with a discussion of the metabolism of just a few peptides in some selected tissues, namely portals of entry (mouth, gastro-intestinal tract, nose, and skin), plasma, organs of elimination (liver, kidney), and pharmacodynamic sites (brain and cerebrospinal fluid). These examples serve as introduction for the presentation in Sect. 6.4.2 of the involvement of individual peptidases in peptide metabolism. 

These CYPs are isoenzymes (or isozymes), catalysing essentially the same reaction, but for different substrate ranges with specificity determined by their different amino acid sequences. CYPs (and other metabolic enzymes) often react with individual substrates in a highly regio-, chemo- or stereo-selective manner, each isozyme displaying its own unique selectivity. Some examples of selective CYP-catalysed transformations are shown in Scheme 1.3. 

---