Pathophysiology 101-823 Unit 4 Metabolism & Metabolic Disease Protein & Amino Acid Metabolism Paul Anderson FALL 2008
Learning Objectives 1. List the metabolic functions of proteins & amino acids. 2. Explain the importance of protein in the human diet and define INCOMPLETE PROTEIN, COMPLETE PROTEIN ESSENTIAL AMINO ACID: NON-ESSENTIAL AMINO ACID 3. Define the AMINO ACID POOL. 4. Define NITROGEN BALANCE and state under what conditions a POSITIVE NITROGEN BALANCE and a NEGATIVE NITROGEN BALANCE occur. 5. State the effects that the following hormones have on protein metabolism, naming the metabolic pathways affected. INSULIN, GLUCAGON, GROWTH HORMONE, GLUCOCORTICOIDS (CORTISOL), SEX HORMONES.THROXINE 6. Define each of the following pathways in protein metabolism and state their importance. TRANSAMINATION: OXIDATIVE DEAMINATION: UREA BIOSYNTHESIS: PROTEIN SYNTHESIS: GLUCONEOGENESIS 7. State the importance of the interconversion of amino acids and intermediates of carbohydrate and lipid metabolism. 8. Distinguish between KETOGENIC and GLUCOGENIC amino acids. References: Porth, Essentials, Ch. 8, p. 167: Ch. 29. pp 634-635: Ch. 32 Porth, Pathophysiology, Ch. 11, p.220 Ch. 43 Martini, Essentials of A & P, Ch. 17
Metabolic Functions of Proteins & Amino Acids Proteins have a variety of structures so have a variety of functions in the body. enzymes, many hormones, antibodies, hemoglobin, cytochromes, support (collagen), movement (actin,myosin) Amino acids form hormones, neurotransmitters. Thyroxine, epinephrine, dopamine (from tyrosine) Amino acids can be a source of energy. Dietary proteins contain about the same amount of energy per gram as carbohydrates. the non-nitrogen part of amino acids can be oxidised directly in cell respiration or after conversion to ketone bodies. Normally about 12% of our daily energy needs come from amino acids. Excessive use of amino acids for energy causes a deficiency of tissue proteins and an excess of ketone bodies.
Dietary Protein, Amino Acid Pool & Metabolic Pathways A normal diet should contain sufficient protein for metabolic needs Complete proteins with 9 essential amino acids which the body cannot synthesize, e.g. phenylalanine. Most plant proteins are incomplete Unlike carbohydrate or fat there is no specific storage depot for proteins or amino acids. Instead the amino acid pool of the blood plasma acts as a reservoir which each tissue can draw upon. Each tissue makes those specific proteins which it needs, controlled by the active genes in that tissue. The liver is the major organ involved in protein metabolism especially for deamination, urea synthesis and gluconeogenesis
Metabolic Pathways of Proteins & Amino Acids Dietary proteins cellular proteins AMINO ACID POOL in plasma transamination α keto acids NH 3 amino acid products deamination urea energy gluconeogenesis glucose ketogenesis ketone bodies Excreted in urine
Nitrogen Balance Nitrogen balance means that N intake (dietary protein) = N output in urine (NH 3, urea, uric acid) N balance is controlled by diet & hormones. Normally hormones control protein anabolism/catabolism to maintain N balance. Dietary proteins Protein Anabolism Anabolic Hormones GH (via IGF) Sex hormones Insulin Thyroxine (children) AMINO ACID POOL Tissue proteins Protein Catabolism GH: Growth Hormone IGF: Insulin like Growth factor Urinary N Catabolic Hormones Glucocorticoids
Nitrogen Imbalance Nitrogen Imbalance means N intake does not equal N output. Positive N balance means N intake > N output with weight gain due to increased tissue protein stimulated by anabolic hormones. Occurs in: -normal growth - Convalescence -Pregnancy Negative N balance means N output > N intake with weight loss due to tissue protein breakdown caused by disease or lack of dietary protein. Occurs in - Starvation - Wasting diseases (cancer, paralysis) - Diabetes mellitus - Excess glucocorticoids (Cushing s syndrome)
Protein & Amino Acid Anabolism PROTEIN SYNTHESIS occurs on ribosomes in every cell and is stimulated by Anabolic Hormones - Insulin-like Growth Factor(IGF) - Thyroxine (in growing children) - Insulin - Estrogen & Testosterone Weight-bearing exercise causes anabolism & growth of muscle. Non essential amino acids can be synthesized by TRANSAMINATION (transfer of an amino group to a keto acid to create an amino acid).
Transamination TRANSAMINATION is the exchange of R groups between amino acids and keto acids forming a new amino acid & keto acid. Transamination builds non essential amino acids in cells by using a keto acid with the desired R group. R R R R R group of α keto acid becomes R group of new amino acid
Protein Mobilisation & Deamination Protein Mobilisation is the widespread breakdown of proteins to amino acids is stimulated by glucocorticoids in starvation & in diabetes mellitus. Liver cells take in amino acids from the amino acid pool and convert glucogenic amino acids into glucose (gluconeogenesis) and ketogenic amino acids into keto acids by deamination. Deamination prepares amino acids for catabolism by removing the amino group (NH 2 ) forming a keto acid. Keto acids produced by deamination or transamination may be - oxidised for energy (in the Krebs cycle) - used in gluconeogenesis (glucogenic amino acids) - converted to acetyl CoA & ketone bodies (ketogenic amino acids) by ketogenesis: ketone bodies are then released into the blood for oxidation by other tissues.
Protein Mobilisation & Fate of Amino Acids Proteins Blood Glucose Protein Mobilisation Tissue Cells Amino acids AMINO ACID POOL in plasma Ketone bodies in blood Glucose Liver Cell NH 3 Amino acids Krebs Cycle Ketone bodies Gluco neogenesis Glucogenic amino acids Deamination Ketoacids Keto genesis
Deamination & Nitrogen Excretion When amino acids are no longer needed they are deaminated by the liver and kidneys removing NH 2 and forming NH 3 in the process of oxidative deamination. The keto acid may be used as a source of energy or for making glucose. oxidative deamination NH 3 Amino acid Keto acid
Formation of Urea Ammonia produced by deamination is highly toxic to the brain. The liver detoxifies NH 3. by converting it to urea excreted by the kidneys. In the Urea Cycle NH 3 combines with CO 2 to form urea.. In advanced liver disease increased blood NH 3 causes mental disturbances and coma. Ammonia UREA Liver Cell Urea Cycle Urea Excreted by kidneys
Summary of Metabolic Pathways 7 8 4 1 5 9 10 Identify Pathways 1-12 11 Ketone bodies 12 6 1 13 13 NH 3 2 13 3 Martini Essentials Figure 17-9
Answers for Metabolic Pathways 1. GLYCOLYSIS 2. KREBS (TCA) CYCLE 3. OXIDATIVE PHOSPHORYLATION 4. GLYCOGENOLYSIS 5. GLYCOGENESIS 6. GLUCONEOGENESIS 7. LIPOLYSIS (LIPID MOBILISATION) 8. LIPOGENESIS 9. PROTEIN HYDROLYSIS (PROTEIN MOBILISATION) 10. PROTEIN SYNTHESIS 11. BETA OXIDATION 12. KETOGENESIS 13. DEAMINATION