Glutamate

 Glutamate, the precursor of the so-called “glutamate family” of amino acids, is formed by the reductive amidation of the citric acid cycle intermediate α-ketoglutarate, a reaction catalyzed by mitochondrial glutamate dehydrogenase (Figure 1). The reaction both strongly favors glutamate synthesis and lowers the concentration of cytotoxic ammonium ion.

Fig1. The reaction catalyzed by glutamate dehydro genase (EC 1.4.1.3).

Glutamine

 The amidation of glutamate to glutamine catalyzed by glutamine synthetase (Figure 2) involves the intermediate formation of γ-glutamyl phosphate (Figure 3). Following the ordered binding of glutamate and ATP, glutamate attacks the γ-phosphorus of ATP, forming γ-glutamyl phosphate and ADP. NH4 + then binds, and uncharged NH3 attacks γ-glutamyl phosphate. Release of Pi and of a proton from the γ-amino group of the tetrahedral inter mediate then allows release of the product, glutamine.

Fig2. The reaction catalyzed by glutamine synthetase (EC 6.3.1.2).

Fig3. γ-Glutamyl phosphate.

Alanine & Aspartate

Transamination of pyruvate forms alanine (Figure 4). Similarly, transamination of oxaloacetate forms aspartate.

Fig4. Formation of alanine by transamination of pyruvate.The amino donor may be glutamate or aspartate. The other product thus is α-ketoglutarate or oxaloacetate.

Glutamate Dehydrogenase, Glutamine Synthetase, & Aminotransferases Play Central Roles in Amino Acid Biosynthesis

 The combined action of the enzymes glutamate dehydrogenase, glutamine synthetase, and the aminotransferases (see Figures 1, 2, and 4) results in the incorporation of potentially cytotoxic ammonium ion into nontoxic amino acids.

Asparagine

 The conversion of aspartate to asparagine, catalyzed by asparagine synthetase (Figure 5), resembles the glutamine synthetase reaction (see Figure 2), but glutamine, rather than ammonium ion, provides the nitrogen. Bacterial asparagine synthetases can, however, also use ammonium ion. The reaction involves the intermediate formation of aspartyl phosphate (Figure 6). The coupled hydrolysis of PPi to Pi by pyro phosphatase, EC 3.6.1.1, ensures that the reaction is strongly favored.

Fig5. The reaction catalyzed by asparagine synthetase (EC 6.3.5.4). Note similarities to and differences from the glutamine synthetase reaction (Figure 2).

Fig6. Aspartyl phosphate.

Serine

Oxidation of the α-hydroxyl group of the glycolytic intermediate 3-phosphoglycerate, catalyzed by 3-phosphoglycerate dehydrogenase, converts it to 3-phosphohydroxypyruvate. Transamination and subsequent dephosphorylation then form serine (Figure 7).

Fig7. Serine biosynthesis. Oxidation of 3-phosphoglycerate is catalyzed by 3-phosphoglycerate dehydrogenase (EC 1.1.1.95). Transamination converts phosphohydroxypyruvate to phosphoserine. Hydrolytic removal of the phosphoryl group catalyzed by phosphoserine hydrolase (EC 3.1.3.3) then forms l-serine.

Glycine

Glycine aminotransferases can catalyze the synthesis of gly cine from glyoxylate and glutamate or alanine. Unlike most aminotransferase reactions, is strongly favored glycine syn thesis. Additional important mammalian routes for glycine formation are from choline (Figure 8) and from serine (Figure 9).

Fig8. Formation of glycine from choline. Catalysts include choline dehydrogenase (EC 1.1.3.17), betaine aldehyde dehydrogenase (EC 1.2.1.8), betaine-homocysteine N-methyltransferase (EC 2.1.1.157), sarcosine dehydrogenase (EC 1.5.8.3), and dimethylglycine dehydrogenase (EC 1.5.8.4).

Fig9. Interconversion of serine and glycine, cata lyzed by serine hydroxymethyltransferase (EC 2.1.2.1).The reac tion is freely reversible. (H4 folate, tetrahydrofolate.)

Proline

The initial reaction of proline biosynthesis converts the γ-carboxyl group of glutamate to the mixed acid anhydride of glutamate γ-phosphate (see Figure 3). Subsequent reduction forms glutamate γ-semialdehyde, which following spontaneous cyclization is reduced to l-proline (Figure 10).

Fig10. Biosynthesis of proline from glutamate. Catalysts for these reactions are glutamate-5-kinase (EC 2.7.2.11), glutamate-5-semialdehyde dehydrogenase (EC 1.2.1.41), and pyrroline 5-carboxylate reductase (EC 1.5.1.2). Ring closure of glutamate semi aldehyde is spontaneous.

Cysteine

 While not itself nutritionally essential, cysteine is formed from methionine, which is nutritionally essential. Following con version of methionine to homocysteine, homocysteine and serine form cystathionine, whose hydrolysis forms cysteine and homoserine (Figure 11). Tyrosine Phenylalanine hydroxylase converts phenylalanine to tyro sine (Figure 12). If the diet contains adequate quantities of the nutritionally essential amino acid phenylalanine, tyrosine is nutritionally nonessential. However, since the phenylalanine hydroxylase reaction is irreversible, dietary tyrosine cannot replace phenylalanine. Catalysis by this mixed-function oxidase incorporates one atom of O2 into the paraposition of phenylalanine and reduces the other atom to water. Reducing power, provided as tetrahydrobiopterin, derives ultimately from NADPH.

Fig11. Conversion of homocysteine and serine to homoserine and cysteine.The sulfur of cysteine derives from methio nine and the carbon skeleton from serine. The catalysts are cystathionine β-synthase (EC 4.2.1.22) and cystathionine γ-lyase (EC 4.4.1.1).

Fig12. Conversion of phenylalanine to tyrosine by phenylalanine hydroxylase (EC 1.14.16.1). 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.

Hydroxyproline & Hydroxylysine

 Hydroxyproline and hydroxylysine occur principally in collagen. Since there is no tRNA for either hydroxylated amino acid, neither dietary hydroxyproline nor dietary hydroxylysine is incorporated during protein synthesis. Peptidyl hydroxyproline and hydroxylysine arise from proline and lysine, but only after these amino acids have been incorporated into peptides. Hydroxylation of peptidyl prolyl and peptidyl lysyl residues, catalyzed by prolyl hydroxylase and lysyl hydroxylase of skin, skeletal muscle, and granulating wounds requires, in addition to the substrate, molecular O2 , ascorbate, Fe2+, and α-ketoglutarate (Figure 13). For every mole of proline or lysine hydroxylated, one mole of α-ketoglutarate is decarboxylated to succinate. The hydroxylases are mixed-function oxidases. One atom of O2 is incorporated into proline or lysine, the other into succinate (see Figure 13). A deficiency of the vitamin C required for these two hydroxylases results in scurvy, in which bleeding gums, swelling joints, and impaired wound healing result from the impaired stability of collagen.

Fig13. Hydroxylation of a proline-rich peptide. Molecular oxygen is incorporated into both succinate and proline. Procollagen-proline 4-hydroxylase (EC 1.14.11.2) thus is a mixed function oxidase. Procollagen-lysine 5-hydroxylase (EC 1.14.11.4) catalyzes an analogous reaction.

Valine, Leucine, & Isoleucine

While leucine, valine, and isoleucine are all nutritionally essential amino acids, tissue aminotransferases reversibly interconvert all three amino acids and their corresponding α-keto acids. These α-keto acids thus can replace their corresponding amino acids in the diet.

Selenocysteine, the 21st Amino Acid

While the occurrence of selenocysteine (Figure 14) in proteins is relatively uncommon, at least 25 human selenoproteins are known. Selenocysteine is present at the active site of several human enzymes that catalyze redox reactions. Examples include thioredoxin reductase, glutathione peroxidase, and the deiodinase that converts thyroxine to triiodothyronine. Where present, selenocysteine participates in the catalytic mechanism of these enzymes. Significantly, the replacement of selenocysteine by cysteine can actually reduce catalytic activity. Impairments in human selenoproteins have been implicated in tumorgenesis and atherosclerosis, and are associated with selenium deficiency cardiomyopathy (Keshan disease).

Fig14. Selenocysteine (top) and the reaction cata lyzed by selenophosphate synthetase (EC 2.7.9.3) (bottom).

Biosynthesis of selenocysteine requires serine, selenate (SeO4 2−), ATP, a specific tRNA, and several enzymes. Serine pro vides the carbon skeleton of selenocysteine. Selenophosphate, formed from ATP and selenate (see Figure 14), serves as the selenium donor. Unlike 4-hydroxyproline or 5-hydroxylysine, selenocysteine arises cotranslationally during its incorporation into peptides. The UGA anticodon of the unusual tRNA called tRNA^Sec 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. tRNA^Sec is first charged with serine by the ligase that charges tRNA^Ser.

Subsequent replacement of the serine oxygen by selenium involves selenophosphate formed by selenophosphate synthetase (see Figure 14). Successive enzyme-catalyzed reactions convert cysteyl-tRNA^Sec to aminoacrylyl-tRNA^Sec and then to selenocysteyl-tRNA^Sec. In the presence of a specific elongation factor that recognizes selenocysteyl-tRNA^Sec, selenocysteine can then be incorporated into proteins..

اخر الاخبار

اخبار العتبة العباسية المقدسة

في موكب العتبتين المقدستين.. المجمع العلمي ينظم محفله القرآني الدولي الأول بالنجف الأشرف

معمل ثلج الكفيل يرفع طاقته الإنتاجية لنحو 3 آلاف قالب يوميّاً خلال زيارة الأربعين

المجمع العلمي ينشر محطاته القرآنية على مختلف الطرق الرئيسة المؤدية إلى كربلاء

مجمع أبي الفضل العباس (عليه السلام) يرفع إنتاج الصمون لأكثر من 25 ألف قطعة يوميًا

المزيد

الآخبار الصحية

قد يؤدي إلى فشل القلب.. تحذير من مسكن آلام يستعمله الملايين

هل الجري يساعد على فقدان الوزن؟.. إليك ما يقوله الخبراء

ماذا يحدث لجسمك عند شرب عصير البطيخ بانتظام؟

علماء يكتشفون أن نقص عنصر غذائي "شائع" قد يسبب الزهايمر

المزيد

الآخبار التكنلوجية

المعادن الحيوية قد تنضب خلال 10 سنوات.. دراسة صادمة ؟

"إنستغرام" يستنسخ خاصية شائعة من منافسه "سناب شات"

رواد فضاء يغادرون محطة الفضاء الدولية بعد مهمة استمرت 5 أشهر

"كريساليس".. سفينة فضائية ستسافر بالبشر إلى أعماق النجوم ؟!

المزيد

مواضيع ذات صلة

ATP & Ubiquitin-Dependent Degradation

Nutritionally Essential & Nutritionally Nonessential Amino Acids

Cholesterol Synthesis, Transport, & Excretion: Clinical Aspects

Cholesterol is Excreted from The Body in The Bile as Cholesterol or as Bile Acids

Cholesterol is Transported Between Tissue in Plasma Lipoproteins

The Cholesterol Balance in Tissues is Tightly Regulated

Cholesterol Synthesis is Controlled by Regulation of HMG-CoA Reductase

Cholesterol is Biosynthesized From Acetyl-CoA

Brown Adipose Tissue Promotes Thermogenesis

Hormones Regulate Fat Mobilization

Adipose Tissue is The Main Store of Triacylglycerol in The Body

Classification of Proteins