Module 7 Protein Turnover PDF

11/07/2024 Module 7 PROTEIN TURNOVER 1 2 1  11/07/2024 PROTEIN TURNOVER continual renewal or replacement of protein; defined by the balance between protein synthes...

11/07/2024 Module 7 PROTEIN TURNOVER 1 2 1  11/07/2024 PROTEIN TURNOVER continual renewal or replacement of protein; defined by the balance between protein synthesis and protein degradation 3 Dietary Protein Digestion 4 2  11/07/2024 The KREBS BiCYCLE 5 HANS ADOLF KREBS a pioneer scientist in the study of cellular respiration (biochemical process in that extracts energy from food and oxygen, then makes it available to drive the processes of life) best known for discovering the citric acid cycle and (1900 - 1981) the urea cycle 6 3  11/07/2024 Fates of amino acids after digestion/absorption 1. Used for the synthesis of proteins, synthesis of other amino acids, and synthesis of other nitrogen-containing compounds 2. Those ingested in excess of what is needed for biosynthesis needs are mainly degraded to produce ATP Amino acid Degradation 1. Removal of nitrogen (α-amino group) by deamination/transamination 2. Carbon skeleton conversion into Krebs cycle intermediates 7 Fate of the α-amino group: Transamination transfer of an amino group from one amino acid to another α-keto acid by transaminase (aminotransferase) 8 4  11/07/2024 Oxidative Deamination amino group is removed from an amino acid, resulting in the formation of a corresponding keto acid and ammonia 9 UREA CYCLE consists of five sequential enzymatic reactions; first 2 reactions take place at the mitochondria and remaining 3 reactions at the cytosol Arginine https://www.news-medical.net/health/The-Urea-Cycle-Step-by-Step.aspx 10 5  11/07/2024 Cytoplasm is the substance between a cell’s membrane (its outside layer) and its nucleus (its core). Cytosol is the fluid part of cytoplasm; Cytoplasm also consists of organelles and other parts, which float in the cytosol. 11 Mitochondrial stage: Carbamoyl phosphate is formed from ammonia and bicarbonate, by carbamoyl phosphate synthetase Citrulline is formed for the condensation of carbamoyl phosphate and ornithine by trans- carbamoylase 12 6  11/07/2024 UREA cycle 13 Cytosolic Stage: Argininosuccinate synthetase condenses citrulline and aspartate to form argininosuccinate Argininosuccinate is broken down into arginine and fumarate by argininosuccinate lyase Arginine is broken down into urea and ornithine by arginase Ornithine translocase transports ornithine into the mitochondria Net Equation: 2 NH3 + CO2 + 3 ATP + 3 H2O ➔ Urea + 2ADP + 4Pi + AMP 14 7  11/07/2024 Urea Cycle MNEMONICS ORANGE Ornithine COLORED Carbamoyl Phosphate CATS Citrulline ALWAYS Aspartate (enters the cycle) ASK Arginosuccinate FOR Fumarate (leaves the cycle) AWESOME Arginine UMBRELLAS Urea (leaves the cycle) 15 Urea Cycle Disorder defect (impaired function) in any of the 5 enzymes in the urea cycle may lead to NH3 accumulation Ammonia is a potent neurotoxin; normal level is below 50 μmol/L Hyperammonemia a metabolic condition characterized by raised levels of NH3; prevalence https://courses.lumenlearning.com/suny-nutrition/chapter/6-41-transamination- is ~1:140,000 deamination-ammonia-removal-as-urea/ 16 8  11/07/2024 Fate of amino acid carbon skeleton: converted into an intermediate of the citric acid cycle once the amino group is removed Glucogenic Amino Acids converted to glucose via a metabolic pathway known as gluconeogenesis become pyruvate or directly enter the TCA cycle without forming Acetyl CoA as intermediate Ketogenic Amino Acids converted to acetoacetyl-CoA or acetyl-CoA can be used for the synthesis of ketone bodies but not glucose 17 Fates of the CARBON Skeletons of Amino Acids 18 9  11/07/2024 KETOGENESIS a metabolic pathway that produces ketone bodies, which provide an alternative form of energy for the body body is constantly producing small amounts of ketone bodies that can make 22 ATP each in normal circumstances, and it is regulated mainly by insulin KETOSIS – a state in which ketone body production is increased when there are decreased carbohydrates or increased fatty acids 19 Ketone Bodies: β-hydroxybutyrate acetoacetate acetone Acetoacetate and β- hydroxybutyrate are the primary ketone bodies in circulation; can be used as fuel in most tissues, except the liver, which lacks thiophorase (an, enzyme needed to metabolize these substrates https://pressbooks.lib.vt.edu/cell bio/chapter/fuel-for-later/ 20 10  11/07/2024 21 22 11  11/07/2024 AMINO ACID CLASSIFICATION based on their CATABOLISM BOTH GLUCO/ GLUCOGENIC KETOGENIC Alanine Glutamine Isoleucine Arginine Histidine Phenylalanine Asparagine Methionine Tyrosine Aspartate Proline Tryptophan Cysteine Serine Glycine Threonine KETOGENIC Glutamate Valine Leucine Lysine 23 Some Human Genetic Disorders related to Amino Acid Metabolism ALBINISM body makes little or none of melanin pigment Approximate incidence: