Metabolism of proteins and amino acids

Transcription

1 BIOQUÍMICA E BIOLOGIA CELULAR António Ascensão, José Magalhães Metabolism of proteins and amino acids Faculdade de Desporto, Universidade do Porto, 1º Ciclo, 1º Ano 202_2013

2 Humans degradation of ingested proteins

3 Nonessential and essential amino acids Nonessential synthesized by body; usually nonessential in diet! Essential not synthesized by body; essential in diet!

4 General amino acid structure and peptide linkage Lateral chain

5 Amino acid structure (some examples ) α carbon Amino group Carboxil group Lateral Chain (R) Glutamate Lysine Histidine Valine

6 Polypeptide and primary protein structure

7 Body s amino acid pool Leave the body Enter the body

8 Amino acids undergo oxidative degradation 1. during normal cellular protein turnover (synthesis and degradation of proteins), when amino acids that are released from protein breakdown are not needed for new proteins synthesis 2. when a diet is rich in proteins and the ingested amino acids exceed the body's needs for protein synthesis (amino acids cannot be stored) 3. during starvation, prolonged intense exercise or uncontrolled diabetes when carbohydrates are either unavailable or not properly utilized (amino acids are used as fuel)

9 Overview of amino acid catabolism in mammals

10 Amino acid energetic-related catabolism

11 Removal of amina group from amino acids (transamination) The effect of transamination is to collect the amino groups from many different amino acids in the form of Glutamate. Glutamate then functions as an amino donor for biosynthetic pathways or for excretion pathways eliminating nitrogenous waste products

12 Transamination and oxidative deamination Transamination Oxidative deamination (only in mitochondria)

13 Transamination and oxidative deamination

14 Transamination and oxidative deamination Transamination Oxidative deamination (only in mitochondria) (excretion as NH 4+, uric acid or urea) α- Ketoglutarate α- Keto acids α- ketoglutarate (ready for metabolism ex. krebs cycle) (ready for metabolism in krebs cycle or glucose synthesis)

15 Common transamination reactions (Amino groups acceptor) TGP Transaminase Glutâmico-Pirúvica (Amino groups acceptor) TGO Transaminase Glutâmico-Oxaloacética

16 Oxidative Deamination (in mitochondria) Occurs essentially in liver mitochondrial matrix Involves NAD + as the oxidizing agent Reaction catalyzed by glutamate dehydrogenase Glutamate dehydrogenase Biosynthesis Urea cycle

17 Glutamate, glutamine and alanine (special cases ) 1. in the cytosol of hepatocytes amino groups are transferred to α- ketoglutarate to form glutamate which enters mitochondria and gives up its amino group to form ammonium (NH 4+ ) (used in biosynthesis of other amino acids, nucleotides or excreted); 2. excess ammonia (toxic compound that must be converted in a non-toxic before exported to liver trough bloodstream) in most other extrahepatic tissues is converted into glutamine and transported to the liver, then into liver mitochondria; 3. in skeletal muscle amino groups are transferred to pyruvate to form alanine which transports them to the liver.

18 Glutamine-related NH 4 + transport from extrahepatic tissues Liver Extrahepatic tissues

19 Glutamine- Glucose cycle Liver kidneys Extrahepatic Tissues Glutamine Amino Acids (NH 4+ ) Glutamate

20 Alanine - glucose cycle (skeletal muscle - liver) (TGP) (TGP)

21 Overview of amino acids metabolization in the liver Transaminases (aminotransferases) TGP Glutamato dehydrogenase Glutaminase

22 Urea cycle and reactions that feed amino groups into cycle (TGO)

23 Metabolic fate of amonium (NH 4+ ) in liver mitochondria Oxidative Deamination

24 Liver urea (2 amino groups) is produced in 5 steps First amino group" 1" Second" amino group" 2" 3" From mitochondria TGO reaction" (see next slide)" Bloodstream until kidneys and excreted in urine" 5" 4" Into" Krebs cycle" Two amino groups"

25 Links between the urea and krebs cycles (Krebs bicycle!) Reduces the energetic cost of urea synthesis (regeneration of oxaloacetate via aspartate) (TGO) Oxaloacetate ( 1 ATP) ( 2.5 ATP) Oxidative Deamination ( 2 ATP)

26 Summary of amino acid catabolism