Non–α-amino acids present in tissues in a free form include β-alanine, β-aminoisobutyrate, and GABA. β-Alanine is also present in combined form in coenzyme A, and in the β-alanyl dipeptides carnosine, anserine, and homocarnosine.

β-Alanine & β-Aminoisobutyrate

 β-Alanine and β-aminoisobutyrate are formed during catab olism of the pyrimidines uracil and thymine, respectively. Traces of β-alanine also result from the hydrolysis of β-alanyl dipeptides by the enzyme carnosinase, EC 3.4.13.20. β-Aminoisobutyrate also arises by transamination of methylmalonate semialdehyde, a catabolite of l-valine.

The initial reaction of β-alanine catabolism is transamination to malonate semialdehyde. Subsequent transfer of coenzyme A from succinyl-CoA forms malonyl-CoA semial dehyde, which is then oxidized to malonyl-CoA and decarboxylated to the amphibolic intermediate acetyl-CoA. Analogous reactions characterize the catabolism of β-aminoisobutyrate. Transamination forms methylmalonate semialdehyde. Disorders of β-alanine and β-aminoisobutyrate metabolism arise from defects in enzymes of the pyrimidine catabolic pathway. Principal among these are disorders that result from a total or partial deficiency of dihydropyrimidine dehydrogenase.

β-Alanyl Dipeptides

 The β-alanyl dipeptides carnosine and anserine (N-methyl carnosine) (Figure 1) activate myosin ATPase (EC 3.6.4.1), chelate copper, and enhance copper uptake. β-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle. Biosynthesis of carnosine is catalyzed by carnosine synthetase (EC 6.3.2.11) in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of β-alanine and subsequent transfer of the β-alanyl moiety to l-histidine.

ATP + β-Alanine → β-Alanyl-AMP + PPi β-Alanyl-AMP + l-Histidine → Carnosine + AMP

Hydrolysis of carnosine to β-alanine and l-histidine is catalyzed by carnosinase. The heritable disorder carnosinase deficiency is characterized by carnosinuria.

Fig1. Derivatives of histidine. Colored boxes sur round the components not derived from histidine. The SH group of ergothioneine derives from cysteine.

Homocarnosine (Figure 1, present in human brain at higher levels than carnosine, is synthesized in brain tissue by carnosine synthetase. Serum carnosinase does not hydrolyze homocarnosine. Homocarnosinosis, a rare genetic disorder, is associated with progressive spastic paraplegia and mental retardation.

γ-Aminobutyrate

 GABA functions in brain tissue as an inhibitory neurotransmitter by altering transmembrane potential differences. GABA is formed by decarboxylation of glutamate by l-glutamate decarboxylase, EC 4.1.1.15 (Figure 2). Transamination of GABA forms succinate semialdehyde, which can be reduced to γ-hydroxybutyrate by l-lactate dehydrogenase, or be oxidized to succinate and thence via the citric acid cycle to CO2 and H2O (Figure 2). A rare genetic disorder of GABA metabolism involves a defective GABA aminotransferase EC 2.6.1.19, an enzyme that participates in the catabolism of GABA subsequent to its postsynaptic release in brain tissue. Defects in succinic semialdehyde dehydrogenase, EC 1.2.1.24 (Figure2) are responsible for 4-hydroxybutyric aciduria, a rare metabolic disorder of GABA catabolism characterized by the presence of 4-hydroxybutyrate in urine, plasma, and cerebrospinal fluid (CSF). No present treatment is available for the accompanying mild-to-severe neurologic symptoms.

Fig2. Metabolism of γ-aminobutyrate. (α-AA, α-amino acids; α-KA, α-keto acids; PLP, pyridoxal phosphate.)

اخر الاخبار

اخبار العتبة العباسية المقدسة

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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

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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