Lecture 17 (2009)

Lecture 17 (2009) - Midterm 2 Results High: Low: Mean:...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Midterm 2 Results High: Low: Mean: 97.5% 16% 58% Standard Deviation: 16.3 Lecture 17 Amino Acid Metabolism Urea Cycle N and S assimilation Last cofactors: THF and SAM Dietary (Exogenous) Proteins Hydrolyzed in digestive system (~100 g/day) Replenish endogenous amino acids (muscle protein) protein Replenish glycogen stores (glucogenic amino acids) Excess intake for ATP production and lipid synthesis Excess nitrogen is excreted (urea, ammonia) ammonia "Nitrogen" balance is typically zero Proteases, Peptidases Dietary Protein (e.g., Trypsin, Pepsin) Amino Acids Blood Liver Hepatocytes (Cytosol) Aminotransferases Amino Acidx + -KGA (PLP-dependent) -Keto Acidx + Glu From and To Mitochondria From cytosol Hepatocytes Glu Dehydrogenase Glu + NAD+ + H2O -KGA + NADH + NH3 Mitochondria Asp Aminotransferase Glu + OAA -KGA + Asp To cytosol Synthesis of Urea from Ammonia and Aspartate The Urea Cycle James Sumner (1926) Urease Freiedrich Whler (1828) Sir Hans Krebs Urea Cycle (1932) TCA Cycle (1937) Detoxification of ammonia GLU + NAD+ + H2O NH3 + HCO3- + 2 ATP 1 2 KGA + 2 ADP + NADH HPO43- + H+ + NH3 + 2- O NH2 O3P O C Carbamoyl-P p. 88 2- O C NH2 3 NH2 C HPO43- The Urea Cycle O O3P O NH2 CH2 CH2 Ornithine CH2 H C COONH3+ 6 NH2+ NH CH2 Citrulline CH2 CH2 H C COONH3+ ATP Aspartate UREA O C NH2 COOHC Fumarate 4 AMP + PPi H2O H 2N H2N C NH2+ COO- Arginine H NH CH2 CH2 CH2 C COONH3+ CH COO5 HN C NH CH CH2 CH2 CH2 COOCH2 ArgininoH C COO- succinate NH3+ p. 88 Carbamoyl-P Synthetase NH3 + HCO3- + 2ATP Carbamoyl-P + 2ADP + Pi amoyl Carbamoyl-P amoyl H2N-Asp OAA Malate Fumarate H2NCNH2 O Mitochondria and Cytosol Ornithine Urea Cycle Amino Acids -KGA C-Skeletons NADH OAA NADH Glu Dehydrogenase Asp Aminotransferase NAD+ Glu NH4+ Urea Cycle H2 N C O NH2 Asp Fumarate Malate NAD+ UCD: Urea Cycle Disorders HCO3 - www.ureacycle.com Urea Cycle Net Reaction ATP Requirement NH3 + HCO3- + Asp + 3ATP Urea + Fumarate + 2ADP + AMP + 4Pi (4 P~bonds cleaved = "4 ATP") But... NADH Generation Glu + NAD+ + H2O -KGA + NADH + NH3 6 ATP (ETC) Malate + NAD+ OAA + NADH Net Gain of 2ATP/Urea Endogenous Proteins A. Normal Protein Turnover (50-200 g/day) Digestive enzymes (pancreas: >30 g/day) Plasma proteins Cell death (e.g., intestinal mucosa, immune system) Intracellular turnover (damaged proteins, enzyme regulation) proteins regulation B. Mobilization of Skeletal Muscle Protein Fasting, exercise, trauma, injury Fasting Gluconeogenesis Malnutrition (diets deficient in essential amino acids) Intracellular Proteolysis Skeletal Muscle Amino Acids Aminotransferases Amino Acidx + -KGA -Keto Acidx + Glu Ala Aminotransferase Glu + Pyr -KGA + Ala To Liver Intracellular Proteolysis Skeletal Muscle Amino Acids Aminotransferases Amino Acidx + -KGA -Keto Acidx + Glu Glu Dehydrogenase Glu + NAD+ + H2O -KGA + NADH + NH3 Glutamine Synthetase NH3 + Glu + ATP ADP + Pi + Gln To Liver To Kidneys Liver Ala Aminotransferase Ala + -KGA Glu + Pyr Glucose NH3 or Asp Glutaminase Urea Gln + H2O Glu + NH3 Kidneys Glutaminase Gln + H2O Glu + NH3 Urine Muscles (other extrahepatic organs) BLOOD Ala Gln In conditions of metabolic acidosis Liver Urea Kidneys NH3 HCO3- Urea The Cori and Alanine Cycle Glycogen Glucose Pyruvate Proteins Muscle Blood Liver Lactate Alanine Lactate Alanine Glycogen Glucose Pyruvate Urea p. 89 Degradation of Amino Acids: Fate of C-Skeletons Glucogenic Amino Acids: C-skeletons are converted to Pyruvate -Ketoglutarate Succinyl-CoA Fumarate Oxaloacetate (OAA) Ketogenic Amino Acids: C-skeletons are converted to Acetyl-CoA Acetoacetate p. 90 Glucose Pyruvate Glucogenic Acetyl-CoA Ketogenic Lipids Ketone Bodies Oxalaoacetate Citrate Malate TCA Cycle Isocitrate Fumarate -Ketoglutarate Succinyl-CoA Amino Acids Only glucogenic Ala, Cys, Gly, Ser, Thr Asp, Asn Met, Thr (humans), Val Arg, Glu, Gln, His, Pro Only ketogenic Leu, Lys Ketogenic and glucogenic Phe, Tyr Trp Ile Common Degradation Product Pyruvate OAA Succinyl-CoA -Ketoglutarate Acetoacetate Fumarate, Acetoacetate Pyruvate, Acetyl-CoA Succinyl-CoA, Acetyl-CoA p. 90 Nitrogen and Sulfur Assimilation (Amino Acid Synthesis) Nitrogen and Sulfur Assimilation (Amino Acid Biosynthesis) LIGHT O2 ATP NADPH CO2 NO3-, N2 SO43- Photosynthesis NADP+ ADP + Pi H2O Light Reactions CO2 Fixation Carbohydrates Amino Acids p. 91 "Bioenergetics" of Macronutrient Assimilation Electronegativity Assimilation O (3.4) N (3.0) S (2.6) C (2.6) H (2.2) P (2.1) NO3 2SO4 - NAD(P)H NAD(P)H + ATP NAD(P)H + ATP Photosynthesis NH3 H2 S CHO (H2) PH3 CO2 H2 O 3PO4 Nitrate Assimiliation and Nitrogen Fixation A. Most Microorganisms, Fungi, and Plants Nitrate Reductase NO3- + NADH + H+ Nitrite Reductase NO2- + 6 Fdred + 8 H+ NH4+ + 2 H2O + 6 Fdox NO2- + NAD+ + H2O B. Biological Nitrogen Fixation (Microorganisms) Nitrogenase N2 + 8e- + 10H+ + 16 ATP + 16 H2O 2 NH3 + 16 ADP + 16 Pi + H2 p. 91 Assimilation of Ammonia Major Pathway for Ammonia Net Assimilation (MO, Fungi, Plants) Glutamine Synthetase (GS) NH3 + Glu + ATP Glutamate Synthase Gln + -KGA + NAD(P)H + H+ 2 Glu + NAD(P)+ Gln + ADP + Pi Glutamate Aminotransferase (also present in animals) Glu + -Keto Acid -KGA + L--Amino Acid Glutamine Amidotransferase (also present in animals) Gln + R-OH or R1-(C=O)-R2 Glu + R-NH2 or R1-(C=NH)-R2 p. 92 Sulfur Assimilation Adenine SO42O O S O P O O O H O O H H H OH OH Adenosine monophosphate sulfate (APS) carrier-S-SO3- carrier AMP 6 Reduced Ferredoxin 6 Oxidized Ferredoxin 2Fdox O HS CH2 CH NH2 O Cysteine Acetate H3C C O H O O CH2 CH C OH C OH 2Fdred carrier-S-S- NH2 O-acetyl serine p. 95 Sulfur Assimilation 2 O Cysteine Acetate H3C C O H OPi CH2 C OH O C OH 3-Phosphoglycerate (3PGA) O CH2 CH C OH NH2 O-acetyl serine NAD+ NADH + H+ O OPi CH2 C O C OH OPi O CH2 CH C NH2 OH OH CH2 CoA Acetyl CoA O CH NH2 C OH Glu Hydroxy-P-pyruvate KG O-phospho-serine H2O Pi Serine p. 95 ...
View Full Document

This note was uploaded on 09/06/2009 for the course BIS 103 taught by Professor Abel during the Spring '08 term at UC Davis.

Ask a homework question - tutors are online