* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download pyruvate
Survey
Document related concepts
Basal metabolic rate wikipedia , lookup
Catalytic triad wikipedia , lookup
Nicotinamide adenine dinucleotide wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
Metalloprotein wikipedia , lookup
Point mutation wikipedia , lookup
Butyric acid wikipedia , lookup
Glyceroneogenesis wikipedia , lookup
Peptide synthesis wikipedia , lookup
Proteolysis wikipedia , lookup
Protein structure prediction wikipedia , lookup
Fatty acid synthesis wikipedia , lookup
Fatty acid metabolism wikipedia , lookup
Genetic code wikipedia , lookup
Citric acid cycle wikipedia , lookup
Biosynthesis wikipedia , lookup
Transcript
TUMS Dr. Azin Nowrouzi Tehran University of Medical Sciences Fate of the C-Skeleton of Amino Acids 2 Outline of catabolism of 20 amino acids Amino acid Products # enzymatic steps Cofactors Glycogenic or Lipogenic Alanine Pyruvate 1 PLP G Glycine Pyruvate 2 N5,N10 CH2 THF G Serine Pyruvate 1 Cysteine Pyruvate 2 Threonine Pyruvate 3 Aspartic acid Oxaloacetate 1 PLP G Asparagine Oxaloacetate 2 PLP G Histidine α-ketoglutarate 5 THFA, PLP G Glutamic acid α-ketoglutarate 1 PLP G G PLP, NADH G G 4 Glutamine α-ketoglutarate 2 PLP G Amino acid Products enzymatic Cofactors steps Glycogenic or Lipogenic Methionine Succinyl CoA 9 ATP, CoA, NAD, biotin, Vit B12 G Valine Succinyl CoA 10 PLP, NAD, CoA, Vit B12 G Isoleucine Succinyl CoA 9 PLP, NAD, CoA, FAD, G, L biotin, Vit B12 Leucine Succinyl CoA, Acetoacetyl coA 6 Thiamin PP, lipoic acid, PLP, CoA, NAD, FAD L Phenylalanine Succinyl CoA, fumarate 7 O2, NADPH, tetrahydrobiopterin G, L Tyrosine Succinyl CoA, Fumerate 6 O2, NADPH, tetrahydrobiopterin G, L Tryptophan Succinyl CoA, Alanine 9 O2, NADPH, NAD G, L Lysine Acetoacetyl CoA, 9 NADPH, NAD, NADP, PLP, CoA, FAD L 5 Degradation of Carbon Skeletons • Seven products result from the catabolism of amino acid carbon skeletons: – oxaloacetate, α-ketoglutarate, pyruvate, fumarate, acetyl coA, acetoacetyl coA, succinyl coA • Glycogenic – Their catabolism produces pyruvate or one of the intermediates of the Crebs cycle. – These are substrates for gluconeogenesis – So they can produce glycogen in liver and muscle. • Lipogenic (or ketogenic) – Their catabolism produces acetoacetate or its precursors acetyl coA or acetoacetyl coA 6 Amino Acids that produce Oxaloacetate Amino Acids that produce α-ketoglutarate Amino Acids that produce Pyruvate Amino Acids that produce Fumarate Phenylketonuria (PKU) Disease • Deficiency of Phe hydroxylase • Occurs in 1:20,000 live births in U.S. • Seizures, mental retardation, brain damage • Treatment: limit phenylalanine intake • Screening of all newborns mandated in all states 11 Amino Acids that produce Acetyl CoA or Acetoacetyl CoA Amino Acids that produce Succinyl CoA Catabolism of Branched Chain Amino Acids Transfer of nitrogen components from tissues to the liver for urea synthesis Fed state 16 Fasting (starvation) (i) For the first 7 days, maintain blood glucose (brain use 65% of glucose 400 - 600 Cal) (ii) > 7 days: Protein proteolysis decreases (protect essential proteins) therefore use over a prolonged period compromises organism. (iii) → Switch to Ketone bodies 17 18 AA are released from muscle during the post- absorptive state (O/N fast). Of the AA released by muscle Ala= 30% & Gln= 25% (total> 50%) But output (Ala+Gln) > abundance in muscle proteins which contain 7-10% Ala & 6% Gln Where does this Ala & Gln come from? 19 (i)Muscle: Protein → Ala + aa aa→ NH4+ + α keto acids α keto acids → Ala (“simplest” aa). ThereforeSources total Ala released > Ala derived from proteins of Alanine (from Muscle) (ii) Liver: Ala → NH4+ + α keto acids NH4+ → urea (iii) As well Glucose → Pyruvate (no N) → Ala (with N) Therefore Ala serves as a vehicle for transport of NH4+ from muscle to liver (NH4+ is generated through breakdown of aa → energy). (iv) Because free NH4+ is very toxic even at low levels therefore Pyruvate + NH4+ → Ala (non-toxic) (v) In liver: NH4+ → urea for excretion 20 Specialized Amino Acid Roles 1. Certain NEAA continue being synthesized even when adequate levels are supplied in diet because of a specialized role 2. ARG → urea synthesis ASP → urea synthesis GLU → conduit for disposal of N 3. ALA & GLN → key role in exchange between tissues (liver & skeletal muscle) 4. Liver: major site gluconeogenesis (AA → Glucose) major site urea synthesis (kidneys to a lesser extent) 5. Skeletal Muscle: 60% total body protein, 50% total body AA pool and is the major source to provide AA 21 carbons → hepatic gluconeogenesis Amino Acid Degradation 1. Removal of alpha-amino groups 2. Nitrogen excretion 3. Fate of carbon skeletons 22 Removal of alpha-amino groups • Mechanisms of –NH2 removal A. Transamination B. Oxidative deamination C. Amino acid oxidases D. Threonine or Serine dehydratase 23 A. Transamination Removal of Nitrogen by aminotransferase 24 B. Oxidative Deamination 25 L- and D- Amino Acid Oxidases • They are present in liver and kidneys. • They have low activity • Their physiologic value is not clear. Amino Acid + H2O α-ketoacid + NH3 D. Amino acid Dehydratase Threonine Urea Serine and Threonine can be Directly Deaminated 27 Fate of Nitrogen in Different Organisms Other excretion products creatinine uric acid 28 Disposal of amino group • • Urea cycle (Krebs-Henseleit cycle) Provides 25-30 g of urea daily for urine formation in the kidneys a) Carbamoyl Phosphate Synthetase b) Ornitine Carbamoyl Transferase c) Argininosuccinate Synthetase d) Argininosuccinate Lyase e) Arginase • Excretion of free ammonia a) Glutamine synthetase b) Glutaminase 29 Ammonium Ion is Converted into Urea Urea cycle 31 The Urea Cycle is Linked to the Citric Acid Cycle NH4+ 32 Amino Acid Metabolism 33