C

a-KA

HO O L-Serine

Pi H2O

Phospho-L-serine

Figure 28-5. Serine biosynthesis. (a-AA, a-amino acids; a-KA, a-keto acids.)

nh3+

nh3+

Choline

Dimethylglycine O

Sarcosine

Betaine aldehyde

NAD+

Betaine

Glycine O

Figure 28-6. Formation of glycine from choline.

L-Glutamate

-NH2 L-Proline

-NH2 L-Proline

NADH

T"

NADH

L-Glutamate-Y-semialdehyde

A2-Pyrrolidine-5-carboxylate

Figure 28-8. Biosynthesis of proline from glutamate by reversal of reactions of proline catabolism.

mocysteine (see Chapter 30), homocysteine and serine form cysteine and homoserine (Figure 28-9).

Tyrosine. Phenylalanine hydroxylase converts phenylalanine to tyrosine (Figure 28-10). Provided that the diet contains adequate nutritionally essential phenylalanine, tyrosine is nutritionally nonessential. But since the reaction is irreversible, dietary tyrosine cannot replace phenylalanine. Catalysis by this mixed-function oxygenase incorporates one atom of O2 into phenylalanine and reduces the other atom to water. Reducing power, provided as tetrahydrobiopterin, derives ultimately from NADPH.

L-Homocysteine

Cystathionine

H4 folate

HO O Serine

Methylene H4 folate

Glycine

Figure 28-7. The serine hydroxymethyltransferase reaction. The reaction is freely reversible. (H4 folate, tetrahydrofolate.)

H3N+ OH

HS O L-Cysteine

L-Homoserine

Figure 28-9. Conversion of homocysteine and serine to homoserine and cysteine. The sulfur of cysteine derives from methionine and the carbon skeleton from

NH3+

NH3+

NH3+

NH3+

Tetrahydro- Dihydro-biopterin biopterin

Tetrahydro- Dihydro-biopterin biopterin

ch2-ch-coo-

L-Phenylalanine

-H2O

CH2-CH-COO-

CH2-CH-COO-

L-Tyrosine a-Ketoglutarate [18O] Succinate a-Ketoglutarate [18O] Succinate

Figure 28-11. The prolyl hydroxylase reaction. The substrate is a praline-rich peptide. During the course of the reaction, molecular oxygen is incorporated into both succinate and proline. Lysyl hydroxylase catalyzes an analogous reaction.

18OH

Figure 28-11. The prolyl hydroxylase reaction. The substrate is a praline-rich peptide. During the course of the reaction, molecular oxygen is incorporated into both succinate and proline. Lysyl hydroxylase catalyzes an analogous reaction.

H2N N

HN H

HN H

Tetrahydrobiopterin

Figure 28-10. The phenylalanine hydroxylase reaction. Two distinct enzymatic activities are involved. Activity II catalyzes reduction of dihydrobiopterin by NADPH, and activity I the reduction of O2 to H2O and of phenylalanine to tyrosine. This reaction is associated with several defects of phenylalanine metabolism discussed in Chapter 30.

Hydroxyproline and Hydroxylysine. Hydroxy-proline and hydroxylysine are present principally in collagen. Since there is no tRNA for either hydroxy-lated amino acid, neither dietary hydroxyproline nor hydroxylysine is incorporated into protein. Both are completely degraded (see Chapter 30). Hydroxyproline and hydroxylysine arise from proline and lysine, but only after these amino acids have been incorporated into peptides. Hydroxylation of peptide-bound prolyl and lysyl residues is catalyzed by prolyl hydroxylase and lysyl hydroxylase of tissues, including skin and skeletal muscle, and of granulating wounds (Figure 28-11). The hydroxylases are mixed-function oxygenases that require substrate, molecular O2, ascorbate, Fe2+, and a-ketoglutarate. For every mole of proline or lysine hy-droxylated, one mole of a-ketoglutarate is decarboxy-lated to succinate. One atom of O2 is incorporated into proline or lysine, the other into succinate (Figure 28-11). A deficiency of the vitamin C required for these hydroxylases results in scurvy.

Valine, Leucine, and Isoleucine. While leucine, valine, and isoleucine are all nutritionally essential amino acids, tissue aminotransferases reversibly inter-convert all three amino acids and their corresponding a-keto acids. These a-keto acids thus can replace their amino acids in the diet.

Selenocysteine. While not normally considered an amino acid present in proteins, selenocysteine occurs at the active sites of several enzymes. Examples include the human enzymes thioredoxin reductase, glu-tathione peroxidase, and the deiodinase that converts thyroxine to triiodothyronine. Unlike hydroxyproline or hydroxylysine, selenocysteine arises co-translation-ally during its incorporation into peptides. The UGA anticodon of the unusual tRNA designated tRNASec normally signals STOP. The ability of the protein synthetic apparatus to identify a selenocysteine-specific UGA codon involves the selenocysteine insertion element, a stem-loop structure in the untranslated region of the mRNA. Selenocysteine-tRNASec is first charged with serine by the ligase that charges tRNASer. Subsequent replacement of the serine oxygen by selenium involves selenophosphate formed by selenophosphate synthase (Figure 28-12).

NH3+

Figure 28-12. Selenocysteine (top) and the reaction catalyzed by selenophosphate synthetase (bottom).

NH3+

NH3+

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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