1. Amino acids - Classifications, Amino acids Physico – Chemical Properties, Protein structure, folding & function, Nitrogen Cycle Nitrogen Balance, Reductive amination Transamination Urea cycle. Glutamate pathway, Serine pathway, Shikimate pathway

2. Catabolic phase of Amino Acids Breakdown of amino acids is called catabolism. Amino acids are converted to alpha keto acids by the removal of nitrogen in the form of ammonia. Ammonia is converted into Urea or it gets incorporated into some other amino acids.

3. The catabolism of amino acids occurs by the following methods  Oxidative deamination  removal of the amino group from the amino acids  Transamination  transfer of amino group from amino acid to alpha keto acid  Decarboxylation  removal of the CO 2 from carboxylic group of amino acids  Transmethylation  transfer of methyl group from one to another compound

4. Transamination (or amino transfer) is a chemical reaction between two molecules. One is an amino acid, which contains an amine (NH 2 ) group. The other is a keto acid, which contains a keto (=O) group. TRANSAMINATION

5. There are multiple transaminase enzymes which vary in substrate specificity. Some show preference for particular amino acids or classes of amino acids as amino group donors, and/or for particular  -keto acid acceptors. Transaminases (aminotransferases) catalyze the reversible reaction at right.

6. Example of a Transaminase reaction:  Aspartate donates its amino group, becoming the  -keto acid oxaloacetate.   -Ketoglutarate accepts the amino group, becoming the amino acid glutamate.

7. In another example, alanine becomes pyruvate as the amino group is transferred to  -ketoglutarate.

8. Transaminases equilibrate amino groups among available  -keto acids. This permits synthesis of non-essential amino acids, using amino groups from other amino acids & carbon skeletons synthesized in a cell. Thus a balance of different amino acids is maintained, as proteins of varied amino acid contents are synthesized. Although the amino N of one amino acid can be used to synthesize another amino acid, N must be obtained in the diet as amino acids (proteins).

9. Essential amino acids must be consumed in the diet. Mammalian cells lack enzymes to synthesize their carbon skeletons (  -keto acids). These include: Isoleucine, leucine, & valine Lysine Threonine Tryptophan Phenylalanine (Tyr can be made from Phe.) Methionine (Cys can be made from Met.) Histidine (Essential for infants.)

10. The process is catalyzed by enzyme transaminase and the coenzyme needed for this reaction is pyridoxal phosphate (PLP), a derivative of vitamin B 6.

11. Reductive amination Reductive amination is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine.aminationcarbonylamineimine The carbonyl group is most commonly a ketone or an aldehyde.ketonealdehyde It is considered the most important way to make amines, and a majority of amines made in the pharmaceutical industry are made this way

12. This method for synthesizing amino acids is biomimetic, mimics the biological process. React an  -ketoacid with ammonia, then reduce the imine with H 2 /Pd. Racemic mixture is obtained.

13. UREA CYCLE

14.  Urea is the chief nitrogenous waste of mammals.  Most of our nitrogenous waste comes from the breakdown of amino acids. This occurs by deamination.amino acids  Deamination of amino acids results in the production of ammonia (NH 3 ).

15.  Ammonia is an extremely toxic base and its accumulation in the body would quickly be fatal.base  However, the liver contains a system of carrier molecules and enzymes which quickly converts the ammonia (and carbon dioxide) into urea.  This is called the urea cycle.

16.  One turn of the cycle: consumes 2 molecules of ammonia consumes 1 molecule of carbon dioxide creates 1 molecule of urea ((NH 2 ) 2 CO regenerates a molecule of ornithine for another turn.  Although our bodies cannot tolerate high conc. of urea, it is much less poisonous than ammonia.  Urea is removed efficiently by the kidneys.

17. 1.Ornithine transcarbamoylase 2. Argininosuccinate synthetase 3. Argininosuccinate lyase 4. Arginase

19.  The urea cycle consists of 4 reactions.  The first reaction is catalyzed by ornithine transcarbamoylase (1) which transfers a carbamoyl group from carbamoyl phosphate to ornithine to form citrulline.  The second reaction is catalyzed by argininosuccinate synthetase (2). This enzyme uses ATP to activate citrulline by forming a citrullyl-AMP intermediate. This intermediate is attacked by the amino group of an aspartate residue to form argininosuccinate.

20.  The third step is catalyzed by argininosuccinate lyase (3) which cleaves argininosuccinate into fumarate and arginine.  The last step is catalyzed by arginase (4) which cleaves arginine to produce urea and ornithine completing the cycle.