Amino acid metabolism - Urea cycle


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anil    on Jan 25, 2012 Says :

VERY IMPORTANT FOR MEDICAL STUDENTS.
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  Notes
 
 
1 : Amino Acid Metabolism 1
2 : Specific Learning Objectives By the end of this lecture, students should be able to describe Transamination Deamination Urea Cycle
3 : Amino Acid Metabolism Proteins are degraded to amino acids Removal of nitrogen is first step in degradation Ammonium is converted into urea C-skeleton enters known pathways Amino acids are made from intermediates of other pathways Amino acids are precursors
4 : 4 Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine
5 : Ammonia Is Incorporated into Glutamate Glutamate dehydrogenase is located in mitochondria.
6 : Glutamine Is a Nitrogen Carrier in Many Biosynthetic Reactions
7 :
8 : Transamination Reactions Transfer of an amino group from an a-amino acid to an a-keto acid In amino acid biosynthesis, the amino group of glutamate is transferred to various a-keto acids generating a-amino acids In amino acid catabolism, transamination reactions generate glutamate or aspartate
9 : Transamination reactions
10 : (next slide)
11 : (from previous slide) Schiff base
12 : Transaminations Glutamate a-Ketoglutarate + + Pyruvate Alanine Glutamate a-Ketoglutarate + + Oxaloacetate Aspartate Glutamate-Pyruvate Aminotransferase (Alanine Transferase ALT) Glutamate-Oxaloacetate Aminotransferase (Aspartate Transferase AST) Blood levels of these aminotransferases, also called transaminases, are important indicators of liver disease
13 : Deamination The removal of amino group from the amino acid Oxidative deamination FMNH2 L-amino acid oxidase FMN
14 : Non – oxidative deamination AA dehydrase Serine/Threonine/Homoserine NH3 + Keto Acids Desulfhydrases Cysteine NH3 + H2S+Pyruvate Histidase Histidine NH3 + urocanate
15 : 15
16 : 16 Amino Acid Metabolism
17 : Protein Turn Over 17 Ubiquitin (8.5 kDa) marks proteins (in eukaryotes) for destruction -> tag Ubiquitin-Activating Enzyme (E1) Ubiquitin-Conjugating Enzyme (E2) Ubiquitin-Protein Ligase (E3)
18 : Protein Turn Over 18 What determines if protein ubiquitinated? -> n-terminal amino acid (N-rule) -> proteins containing PEST sequence Phosphorylation of PEST domains activates ubiquitination Glycosylation of some PEST proteins with N-acetylglucosamine (GlcNAc) has the opposite effect, prolonging the half-life of these proteins. -> Some proteins (e.g., mitotic cyclins involved in regulation of the cell cycle) have a sequence called a destruction box that is recognized by a domain of the corresponding Ubiquitin Ligase.  A chain of four or more ubiquitins targets proteins for degradation in proteasomes.
19 : Protein Turn Over 19
20 : Protein stability Short lived, Hb, Crystalline Ubiquitination- Tumour Supressor Protein P53 Cervical Carcinoma Bortezomib -- inhibitor of proteasome---multiple myeloma Oxathiazol-2 one-----inhibit inhibitor of Mtb proteasome 20
21 : 21
22 : 22 Fate of Nitrogen in Different Organism
23 : 23 Amino Acid Degradation 1st Step -> Removal of Nitrogen
24 : 24 Amino Acid Degradation Removal of Nitrogen by aminotransferase Prosthetic group involved in amino transfer
25 : 25 Serine and Threonine can be Directly Deaminated Threonine Urea
26 : 26 Ammonium Ion is Converted into Urea Urea cycle
27 : 27 Ammonium Ion is Converted into Urea
28 :
29 : 29 The Urea Cycle is Linked to the Citric Acid Cycle NH4+
30 : 30
31 : Thank you 31
32 : 32 Fate of the C-Skeleton of Amino Acids
33 : 33 Fate of the C-Skeleton of Amino Acids Aromatic amino acids need oxygenases + O2
34 : 34 Major Ammonium ion carrier Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine
35 : 35 Biosynthesis of Amino Acids
36 : 36 Biosynthesis of Amino Acids in Bacteria and Plants Essential ones are in bold letters
37 : 37 Biosynthesis of Amino Acids in Bacteria and Plants
38 : 38 In Mammals Plants and bacteria can produce all of them
39 : Feedback inhibition regulates amino acid biosynthesis 39
40 : Amino acids are precursors 40
41 : Amino acids are precursors 41
42 : Amino acids are precursors 42 Heme degradation: -> bilirubin responsible for color of bruises

 

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