Hydroxylysine, biosynthesis

Humans can synthesize 12 of the 20 common amino acids from the amphiboHc intermediates of glycolysis and of the citric acid cycle (Table 28-1). While nutritionally nonessenrial, these 12 amino acids are not nonessential. AH 20 amino acids are biologically essential. Of the 12 nutritionally nonessential amino acids, nine are formed from amphibolic intermediates and three (cysteine, tyrosine and hydroxylysine) from nutritionally essential amino acids. Identification of the twelve amino acids that humans can synthesize rested primarily on data derived from feeding diets in which purified amino acids replaced protein. This chapter considers only the biosynthesis of the twelve amino acids that are synthesized in human tissues, not the other eight that are synthesized by plants. 

Cysteine, tyrosine, and hydroxylysine are formed from nutritionally essential amino acids. Serine provides the carbon skeleton and homocysteine the sulfur for cysteine biosynthesis. Phenylalanine hydroxylase converts phenylalanine to tyrosine. 

The triplet Cly-X-Y is constantly repeated in the sequence of the triple-helical regions— i. e., every third amino acid in such sequences is aglycine. Proline (Pro) is frequently found in positions X or Y the Y position is often occupied by 4-hydroxyproline (4Hyp), although 3-hydroxyproline (3Hyp) and 5-hydroxylysine (5Hyl) also occur. These hydroxylated amino acids are characteristic components of collagen. They are only produced after protein biosynthesis by hydroxylation of the amino acids in the peptide chain (see p. 62). 

Figure 4. Possible routes of biosynthesis of cross-linkages in collagen. L, lysine HL, hydroxylysine Hi, histidine definition of other symbols in Table II. (Based on data presented in Refs. 59 and 60).

Biosynthesis catabolism Lys is formed in plants and bacteria from meso-2,6- diaminopimelic acid by diaminopimelate decarboxylase (EC 4.1.1.20). The catabolism proceeds through eleven enzymatic steps to acetoacetic acid (acetyl-CoA). L. is a precursor of the cadaverines. Because of its two amino groups it has a cross-linking function in polypeptides such as collagen and elastin, see also 5-hydroxylysine. L. is used as a fodder additive. 

Hydroxylysine, Another glycoprotein which has been studied from the point of view of structure and biosynthesis is collagen. 

The sugar residue of collagen and of kidney glomerular basement membrane is joined to hydroxylysine as follows Glc-a.1.2-Gal-3-Hyl. Studies on the biosynthesis have shown that the transfer is direct from the corresponding uridine nucleotides. 

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... 

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