Amino acid metabolism - Alanine+cysteine

<<Alanine<<

• non-essential
• glucogenic

from pyruvate

Functions and derivatives:

• oxidized to CO2, H2O, energy
• converted to glucose
• Alanine-pyruvate shuttle

<<Cysteine<<

Synthesis

• serine
• cystine (reduction)

Catabolism of cysteine to pyruvate by:

• __cysteine sulfinate__ (major pathway, oxidation)
• cysteine desulfhydrase (direct deamination)
• direct transamination

Functions and derivatives:

• one of 20 $primary$ amino acids of proteins
• converted to $pyruvate$ (glucogenic)
• catabolized or utilized for producing $energy$
• formation of $thioethanolamine$ (component of CoASH and ACP (acyl carrier protein)
• synthesis of $taurine$ (precursor for bile salts)
• synthesis of cystine, formation of disulfide bonds that stabilize tertiary structure of proteins
    * e.g. insulin, keratin, immunoglobulins
• active site of many enzymes (thiol group of cystiene)
    * e.g. glyceraldehyde-3-phosphate dehydrogenase, fatty acid synthase multienzyme complex
• H2S by desulfhydrase is the source of active sulfate (PAPS) ,used for synthesis of
    * GAGS, Sulfolipids, in detoxification of indols

Fates of homocyteine

• conversion to $methionine$ (salvage)
• synth. of $cysteine$
• direct deamination to $α-keto butyrate$
• synth. of $glutathione$ (non ribosomal)

Important functions of glutathione:

• transport of amino acids through cell membranes
• antioxidant (removal H2O2)
• coenzyme for:
    * maleylacetoacetate isomerase
    * glutathione-insulin transhydrogenase
• reduction of the thiol group of many proteins
• detoxication of many toxic compounds
    * bromobenzene

Metabolic inborn errors of cysteine and cystine metabolism

cytsinuria

• ==inherited metabolic disease==
• defect in $renal reabsorptive mechanism of <strong>4 amino acids</strong>$:
    * cystine
    * lysine
    * arginine
    * ornithine
• amino acids excreted in urine in increased amounts
• $cystine stones$ formed in renal tubules

cystinosis (cystine storage disease)

• rare ==lysosomal disorder==
• $defect carrier$ mediated $transport of cystine$
• cystine is deposited as crystals in tissues and organs = damage of affected organ
• ==patient may die from renal failure==