Alanine

 Alanine serves as a carrier of ammonia and of the carbons of pyruvate from skeletal muscle to liver via the Cori cycle, and together with glycine constitutes a major fraction of the free amino acids in plasma.

Arginine

 Figure 1 summarizes the metabolic fates of arginine. In addition to serving as a carrier of nitrogen atoms in urea bio synthesis, the guanidino group of argi nine is incorporated into creatine, and following conversion to ornithine, its carbon skeleton serves as a precursor of the polyamines putrescine and spermine.

Fig1. Arginine, ornithine, and proline metabolism. Reactions with solid arrows all occur in mammalian tissues. Putrescine and spermine synthesis occurs in both mammals and bacteria. Arginine phosphate of invertebrate muscle functions as a phosphagen analogous to creatine phosphate of mammalian muscle.

The reaction catalyzed by nitric oxide synthase, EC 1.14.13.39 (Figure 2), a five-electron oxidoreductase with multiple cofactors, converts one nitrogen of the guanidine group of arginine to nitric oxide, an intercellular signaling molecule that serves as a neurotransmitter, smooth muscle relaxant, and vasodilator.

Fig2. The reaction catalyzed by nitric oxide synthase.

Cysteine

 Cysteine participates in the biosynthesis of coenzyme A by reacting with pantothenate to form 4-phosphopantothenoylcysteine. In addition, taurine, formed from cystreine, can displace the coenzyme A moiety of cholyl CoA to form the bile acid taurocholic acid . The conversion of cysteine to taurine involves catalysis by the nonheme Fe2+ enzyme cysteine dioxygenase (EC 1.13.11.20), sulfinoalanine decarboxylase (EC 4.1.1.29), and hypotaurine dehydrogenase (EC 1.8.1.3) (Figure3).

Fig3.  Conversion of cysteine to taurine. The reactions are catalyzed by cysteine dioxygenase, cysteine sulfinate decarboxylase, and hypotaurine decarboxylase, respectively.

Glycine

Many relatively apolar metabolites are converted to water-soluble glycine conjugates. An example is the hippuric acid formed from the food additive benzoate (Figure 4). Many drugs, drug metabolites, and other compounds with  carboxyl groups also are conjugated with glycine. This makes them more water soluble and thereby facilitates their excretion in the urine.

Fig4. Biosynthesis of hippurate . Analogous reactions occur with many acidic drugs and catabolites.

Glycine is a component of creatine, and its nitrogen and α-carbon are incorporated into the pyrrole rings and the methylene bridge carbons of heme. The entire glycine molecule supplies atoms 4, 5, and 7 of the purine bases.

Histidine

 Decarboxylation of histidine to histamine is catalyzed by the pyridoxal 5′-phosphate-dependent enzyme histidine decarboxylase, EC 4.1.1.22 (Figure 5). A biogenic amine that functions in allergic reactions and gastric secretion, histamine is present in all tissues. Its concentration in the brain hypothalamus varies in accordance with a circadian rhythm.

Fig5. The reaction catalyzed by histidine decarboxylase.

Histidine-containing compounds present in the human body include carnosine, and dietarily derived ergothioneine and anserine (Figure 6). Carnosine (β-alanyl-histidine) and homocarnosine (γ-aminobutyryl-histidine) are major constituents of excitable tissues, brain, and skeletal muscle. Urinary levels of 3-methylhistidine are unusually low in patients with Wilson disease.

Fig6. Derivatives of histidine. Colored boxes sur round the components not derived from histidine. The SH group of ergothioneine derives from cysteine.

Methionine

 The major nonprotein fate of methionine is conversion to S-adenosylmethionine, the principal source of methyl groups in the body. Biosynthesis of S-adenosylmethionine from methionine and ATP is catalyzed by methionine adenosyltransferase (MAT), EC 2.5.1.6 (Figure 7). Human tissues contain three MAT isozymes: MAT-1 and MAT-3 of liver and MAT-2 of nonhepatic tissues. Although hyper methioninemia can result from severely decreased hepatic MAT-1 and MAT-3 activity, if there is residual MAT-1 or MAT-3 activity and MAT-2 activity is normal, a high tissue concentration of methionine will ensure synthesis of adequate amounts of S-adenosylmethionine.

Fig7. Biosynthesis of S-adenosylmethionine, catalyzed by methionine adenosyltransferase.

Following decarboxylation of S-adenosylmethionine by methionine decarboxylase (EC 4.1.1.57), three carbons and the α-amino group of methionine can be utilized for the biosynthesis of the polyamines spermine and spermidine. These polyamines function in cell proliferation and growth, are growth factors for cultured mammalian cells, and stabilize intact cells, subcellular organelles, and membranes. Pharmacologic doses of polyamines are hypothermic and hypotensive. Since they bear multiple positive charges, polyamines readily associate with DNA and RNA. Figure 8 summarizes the biosynthesis of polyamines from methionine and ornithine, and Figure 9 the catabolism of polyamines.

Fig8. Intermediates and enzymes that participate in the biosynthesis of spermidine and spermine.

Fig9. Catabolism of polyamines.

Serine

 Serine participates in the biosynthesis of sphingosine, and of purines and pyrimidines, where it pro vides carbons 2 and 8 of purines and the methyl group of thymine. Genetic defects in cystathionine β-synthase (EC 4.2.1.22)

Serine + Homocysteine → Cystathionine + H₂O

a heme protein that catalyzes the pyridoxal 5′-phosphate dependent condensation of serine with homocysteine to form cystathionine, result in homocystinuria. Finally, serine (not cysteine) serves as the precursor of peptidyl selenocysteine.

Tryptophan

 Following hydroxylation of tryptophan to 5-hydroxytryptophan by liver tryptophan hydroxylase (EC 1.14.16.4), subsequent decarboxylation forms serotonin (5-hydroxytryptamine), a potent vasoconstrictor and stimulator of smooth muscle con traction. Catabolism of serotonin is initiated by deamination to 5-hydroxyindole-3-acetate, a reaction catalyzed by monoamine oxidase, EC 1.4.3.4 (Figure 10). The psychic stimulation that follows administration of iproniazid results from its ability to prolong the action of serotonin by inhibiting monoamine oxidase. In carcinoid (argentaffinoma), tumor cells overproduce serotonin. Urinary metabolites of serotonin in patients with carcinoid include N-acetylserotonin glucuronide and the glycine conjugate of 5-hydroxyindoleacetate. Serotonin and 5-methoxytryptamine are metabolized to the corresponding acids by monoamine oxidase. N-Acetylation of serotonin, followed by its O-methylation in the pineal body, forms melatonin. Circulating melatonin is taken up by all tissues, including brain, but is rapidly metabolized by hydroxylation followed by conjugation with sulfate or with glucuronic acid. Kidney tissue, liver tissue, and fecal bacteria all convert tryptophan to tryptamine, then to indole 3-acetate. The principal normal urinary catabolites of tryptophan are 5-hydroxyindoleacetate and indole 3-acetate (Figure 10).

Fig10. Biosynthesis and metabolism of serotonin and melatonin. ([NH4+], by transamination; MAO, monoamine oxidase; ~CH3 , from S-adenosylmethionine.)

Tyrosine

 Neural cells convert tyrosine to epinephrine and norepi nephrine (Figure 11). While dopa is also an intermediate in the formation of melanin, different enzymes hydroxylate tyrosine in melanocytes. DOPA decarboxylase (EC 4.1.1.28), a pyridoxal phosphate-dependent enzyme, forms dopamine. Subsequent hydroxylation, catalyzed by dopamine β-oxidase (EC 1.14.17.1), then forms norepinephrine. In the adrenal medulla, phenylethanolamineN-methyltransferase (EC 2.1.1.28) utilizes S-adenosylmethionine to methylate the primary amine of norepinephrine, forming epinephrine (Figure 11). Tyro sine is also a precursor of triiodothyronine and thyroxine.

Fig11. Conversion of tyrosine to epinephrine and norepinephrine in neuronal and adrenal cells. (PLP, pyridoxal phosphate.)

Phosphoserine, Phosphothreonine, & Phosphotyrosine

 The phosphorylation and dephosphorylation of specific seryl, threonyl, or tyrosyl residues of proteins regulate the activity of certain enzymes of lipid and carbohydrate metabolism and of proteins that participate in signal transduction cascades.

Sarcosine (N-Methylglycine)

 The biosynthesis and catabolism of sarcosine (N-methylglycine) occur in mitochondria. Formation of sarcosine from dimethyl glycine is catalyzed by the flavoprotein dimethyl glycine dehydrogenase EC 1.5.8.4, which requires reduced pteroylpenta glutamate (TPG).

Dimethylglycine + FADH₂ + H₄TPG + H₂O → Sarcosine +N-formyl-TPG

Traces of sarcosine can also arise by methylation of glycine, a reaction catalyzed by glycine N-methyltransferase, EC 2.1.1.20.

Glycine + S-Adenosylmethionine → Sarcosine +S-Adenosylhomocysteine

Catabolism of sarcosine to glycine, catalyzed by the flavoprotein sarcosine dehydrogenase EC 1.5.8.3, also requires reduced TPG.

Sarcosine + FAD + H₄TPG + H₂O → Glycine + FADH₂ +N-formyl-TPG

The demethylation reactions that form and degrade sarcosine represent important sources of one-carbon units. FADH2 is reoxidized via the electron transport chain.

Creatine & Creatinine

Creatinine is formed in muscle from creatine phosphate by irreversible, nonenzymatic dehydration, and loss of phosphate (Figure12). Since the 24-hour urinary excretion of creatinine is proportionate to muscle mass, it provides a measure of whether a complete 24-hour urine specimen has been collected. Glycine, arginine, and methionine all participate in creatine biosynthesis. Synthesis of creatine is completed by methylation of guanidoacetate by S-adenosylmethionine (Figure 12).

Fig12. Biosynthesis of creatine and creatinine. Conversion of glycine and the guanidine group of arginine to creatine and creatine phosphate. Also shown is the nonenzymic hydrolysis of creatine phosphate to creatinine.

اخر الاخبار

اخبار العتبة العباسية المقدسة

مع وصول الزيارة ذروتها.. العتبة العباسية المقدسة تستنفر ملاكاتها لخدمة زائري مرقدي الإمامين العسكريين (عليهما السلام)

قسم الشؤون الطبية: الخطة الخدمية في سامراء تضمنت مشاركة نحو ٥٠ متطوعًا من ثلاث محافظات

عبر محطات الإجابة عن الاستفتاءات الشرعية مشروع التبليغ الحوزوي يقدّم خدماته لزائري مدينة سامراء

قسم حفظ النظام يشارك في تأمين زيارة الإمام الحسن العسكري (عليه السلام) بمدينة سامراء

المزيد

الآخبار الصحية

دون آثار جانبية.. زيت عشبة طبيعية قد يعالج القلق

"ليكانيماب".. علاج الزهايمر يطرح رسميا في السوق الألمانية

متى يجب تنظيف الأسنان في الصباح.. قبل أم بعد الإفطار؟

ارتفاع الوفيات.. منظمة الصحة تدق جرس الإنذار بشأن الكوليرا

المزيد

الآخبار التكنلوجية

أكبر مشروع طاقة رياح في نصف الكرة الجنوبي يحقق إنجازين جديدين

5 أمور لا تفعلها أثناء تشغيل مكيف سيارتك

ضوء إدارة المحرك: أسئلة مهمة لفهم عمله ومعانيه

"واتساب" يطلق خاصية جديدة لكتابة الرسائل بالذكاء الاصطناعي

المزيد

مواضيع ذات صلة

The Deoxyribonucleosides of Uracil & Cytosine are Salvaged

Biosynthesis of Pyrimidine Nucleotides

Hepatic Purine Biosynthesis is Stringently Regulated

Inosine Monophosphate (IMP) is Synthesized From Amphibolic Intermediates

DNA & RNA are Polynucleotides

Synthetic Nucleotide Analogs are Used in Chemotherapy

Chemistry of Purines, Pyrimidines, Nucleosides, & Nucleotides

Disorders of Bilirubin Metabolism

Catabolism of HEME Produces Bilirubin

Disorders of Heme Biosynthesis

Porphyrins are Colored & Fluoresce

Heme is Synthesized From Succinyl-CoA & Glycine