HNF 461 Exam 3 Study Guide Lectures 28 32 Lecture 28 and 29 November 6 and 13 Hepatic Amino Acid Metabolism 1 The liver clears 50 65 of dietary amino acids In general what does the liver use free amino acids for In other words what is the fate of those dietary amino acids absorbed by the liver You should be able to describe their use in general a Small percentage of amino acids absorbed by the liver will be used to synthesize proteins and N containing compounds b The rest of the amino acids absorbed by the liver will be used for energy metabolism processes 2 Know the physiological function of the few amino acid derived nitrogen containing compounds discussed in class glutathione carnitine creatine carnosine and choline a Glutathione tripeptide antioxidant scavenges free radicals b Carnitine transporter of long chain FAs from the cytosol into the mitochondria for beta oxidation c Creatine phosphorylation to create phosphocreatine contains high energy bond for short term energy d Carnosine most abundant in the muscle and stores histidine functions as a buffer and maintains osmolarity in muscle cells e Choline a functional part of lecithin and acetylcholine 3 Know the few amino acid derived hormones discussed in class catecholamines serotonin and histamine a Serotonin made from tryptophan b Thyroid hormone made from tyrosine c Epinephrine made from tyrosine d Catecholamines especially norepinephrine and epinephrine are involved in metabolic regulation They are stress hormones that increase catabolism e Catecholamines serotonin and histamine are all neurotransmitters 4 What sources contribute to the body s free amino acid pool a Dietary protein b Endogenous protein 5 How does the size of this free amino acid pool compare to the total protein in the body a The free amino acid pool 100g is much smaller compared to the total protein in the body 6 Why does essential amino acid deficiency result in negative nitrogen balance a Protein synthesis cannot continue when n amino acid is missing The unfinished peptide product will be degraded and free amino acids get oxidized 7 In what tissue are the branch chain amino acids metabolized for energy a Metabolized in skeletal muscle tissue 8 Understand transamination What does it start with and what does it produce a Transamination starts with one amino acid and one keto acid b Transfer of amino group from amino acid to keto acid c Produces a new amino acid and a new keto acid d Ex Alanine amino acid and alpha ketoglutarate keto acid pyruvate keto acid and glutamate amino acid 9 Know that the amino acids that can be metabolized into any TCA cycle intermediates or pyruvate are glucogenic Those that become acetyl CoA or acetoacetate are ketogenic Understand why a Everything from the TCA cycle that can be converted to oxaloacetate pyruvates or intermediates is glucogenic because oxaloacetate will be converted to glucose b Amino acids that become acetyl CoA or acetoacetate are ketogenic because they can never become glucose 2 carbons from acetyl CoA are lost as CO2 10 What reaction produces ammonia Do we want ammonia build up in the blood a Deamination most commonly of glutamate produces ammonia b Cannot allow free ammonia to build up in the blood because large amounts can become toxic for the brain i Maintaining ammonia levels excretion of ammonia in urine or excretion of ammonium ammonia H in urine 11 Does the urea cycle require energy What does it produce Where does the nitrogen in urea come from a The urea cycle is a very energy consuming process i Conversion of ammonia to carbamoyl PO4 requires 2ATP ii Conversion of aspartate to arginino succinate requires ATP b Produces urea i NH3 carbamoyl PO4 ii Carbamoyl PO4 ornithine citrulline leaves mitochondria and travels to cytoplasm iii Citrulline aspartate arginine succinate iv Arginino succinate arginine v Arginine ornithine releases urea c One source of nitrogen in urea comes from an amino acid usually aspartate the second source of nitrogen comes from free ammonia most commonly from glutamate deamination in the liver 12 Name two amino acids that carry nitrogen out from muscle to the liver What happens to their nitrogen in the liver a Glutamine gives away its amino group in the liver for urea synthesis the carbon skeleton a ketoglutarate can enter the TCA cycle for energy or gluconeogenesis b Alanine gives away its amino acid group in the liver for urea synthesis the carbon skeleton pyruvate can enter the TCA cycle for energy or gluconeogenesis 13 When glutamine is produced and released by the muscle it can be taken up by the liver the intestinal cells or the kidneys a What may the liver use glutamine for i Glutamine gives away its nitrogen group to produce urea b What do the enterocytes need glutamine for i Use both glutamine and glutamate to make their own protein ii Most becomes oxidized and becomes CO2 in the TCA cycle to produce energy c When blood pH is low the kidney will use more glutamine Why i Conversion of glutamine directly to urea ii Urea is basic so it will neutralize the acidity of blood when pH is low 14 Glutamine is also important for the rapidly dividing growing cells such as the enterocytes and immune cells Why a Glutamine is required for nucleotide synthesis and required to make new proteins b Rapidly dividing cells need to make new DNA RNA and proteins Lecture 30 November 15 Protein Requirement and Turnover Dietary Protein Quality 15 What hormones promote N retention protein synthesis and what hormones promote protein catabolism a Insulin and growth hormone promote N retention protein synthesis b Glucocorticoids glucagon and epinephrine promote protein catabolism 16 What is protein turnover Does it contribute to BMR RMR a Protein turnover the balance between protein synthesis and protein degradation b Resting metabolic rate accounts for 60 total energy expenditure i 10 25 of this percentage will be used for protein turnover 17 What determines protein quality Is amino acid composition the only factor a Amino acid composition complete or incomplete proteins i Amino Acid Score AAS comparison between tested proteins for amino acid composition and a standard protein b Protein Digestibility Corrected AAS PDCAAS takes into account how well a protein can be digested i Something may have high protein content but if our bodies can t digest the protein it is no use to us Lecture 31 November 18 Determining Protein Requirement 18 Know how much nitrogen proteins have on average and how much