Sulphur containing amino acids metabolism

Sulphur containing amino acids metabolism

• 1.
  Metabolism of sulfur containingamino acids Methionine and Cysteine Dr. Dhiraj J. Trivedi
• 2.
  Metabolism of sulphur containingamino acids • Methionine and Cysteine are sulphur containing Amino acids • Methionine is essential amino acid • Cysteine can be synthesized by transfer of sulphur group from methionine to hydroxyl group of serine. • Cysteine is non essential in presence of methionine.
• 3.
  Three major metabolicroute 1. Methionine for transmethylation 2. Methionine for Cysteine synthesis 3. Cysteine to specialized products.
• 4.
  Over view ofMethionine metabolism Methionine Cysteine Transmethylation Cystathionine Polyamines Proteins Spermin and spemidine
• 5.
  Methionine for transmethylation Homocysteinuria -III Homocysteinuri a - II Methionine ATP S- adenosyl Methionine (SAM) Methionine adenosyl transferase PPi + Pi S- adenosyl homocysteine SAHC Methylated Product Methyl transferase Methyl acceptor Homocysteine AdenosineH2O S- adenosyl homocysteinase THF Methionine Synthetase N5 Methyl THF N5 Methyl THF Reductase B12 Homocysteinuria - I Cystathionine B6P Cystathionin e synthease
• 6.
  Synthesis of Cystathionine Serine Cystathionine Cystathionine synthase H2O Homocysteine B6P Homocysteinuria - I
• 7.
  Synthesis of Cysteineand succinyl CoA Trans- sulphuration Followed by Deamination When excess of methionine is present carbons can be used for energy and sulphur is retained in Cysteine Serine Cystathionine Cystathionine synthaseH2O α –Keto butyrate NH3 Cystathionase Homocysteine Cystein e B6 P B6 P Propionyl CoA KBDH CO2 CoASH H2O Cystathioninuri a NAD+ NADH + H
• 8.
  Catabolism of Cysteine •Cysteine derived form Homocysteine and Serine is metabolized by various route depending on the need of the cell. • Major metabolism is Cysteinesulfinate pathway. • It synthesize Taurine as end product, Pyruvate is made free • Taurine is intracellular free amino acid, metabolic amino acid. • It is used for conjugation of bile acids , • Taurine also play role as neurotransmitter. • Cysteine forms Coenzyme A with pantothenica acid
• 9.
  Over view ofCysteine metabolism Methionine Cysteine Proteins Glucose Fat Glutathione Taurine Coenzyme A Active sulfate
• 10.
  Cysteine Mercapto Ethanolamine CO2 Coenzyme A Pantothenic acid Sulfinate pathway SO4 Phosphoadenosine phosphosulfate ATP Activesulfate Puruvate H2 S NH3 Desulfuras e Taurine
• 11.
  Cysteine to Thiosulfate& CoA Cysteine Mercapto Pyruvate Thiosulfate SO3 Pyruvate α-K G Glutamate Amino transferase MercaptoPyruvate sulfutransferase Used for detoxication of cyanide Mercapto Ethanolamine CO2 Coenzyme A Pantothenic acid Decarboxylase
• 12.
  Cysteine to Thiocysteine Cysteine Thiocysteine Cysteine NH4 Pyruvate H2O Usedfor detoxication of cyanide Cystathionase
• 13.
  Cysteine to Taurine& Sulfate Cysteine Cysteine Sulfinate Hypotaurine Taurine Pyruvate α-K GGlutamate Bisulfite In Urine SO4 Cysteine Dioxygenase Decarboxylase CO2 O2 Oxidation Trans desulfuration Oxidation
• 14.
  Cysteine to ActiveSulfate Cysteine Cysteine Sulfinate Sulfat e Pyruvate Pyruvate Alanine PAPS Cysteine Dioxygenase O2 Desulfuration Transaminase β-Sulfinyl Pyruvate ATPActive Sulfate
• 15.
  Inborn errors ofSulfur amino acids • 1. Cystinuria (Cystin-Lysinuria ) : – Defect in renal tubular protein carrier • 2. Cystinosis : Storage disorder – Defect in lysosomal enzyme • 3. Homocystinuria (1 in 200,000) Defect in – Type I  Cystathionine synthetase – Type II  THF Synthetase, Methionine synthetase – Type III  THF Reductase , (B12 ) • 4. Cystathioninuria – Deficiency of Cystathionase (Also B6P may cause )
• 16.
  Polyamines • Decarboxylated Ornithineis a four carbon di-amine. That is a precursor of spemidine and spermine (polyamines) • Polyamines were first discovered from semen • Now they are found associated with nucleic acids in almost all cells. • Their exact functions are not known.
• 17.
  Homocystinuria • Autosomal recessivetype of Group of disorders • Defect in metabolism of Homocysteine, Methionine • Characterized by high plasma and urinary levels of homocysteine and methionine. But low level of Cysteine. • Deficiency of B6 dependent enzyme Cystathionine –β- synthetase • Octopia lentis (displacement of lense of the eye) is cardinal sign. • Skeletal abnormalities, Premature arterial disease, Osteoporosis, mental retardation are additional symptoms. • Tretment: Restriction of methionine intake, mega dose of B6, B12 and folic acid.
• 18.
  Cystathioninuria • Disorder ofsulfur containing amino acid • Deficiency of cystathionase • Accumulation of cystathionine and its metabolites in plasma. • No clinical symptoms.
• 19.
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