Protein metabolism - Denotes the various biochemical processes responsible for the synthesis of proteins and amino acids

including the breakdown of proteins (and other large molecules) by catabolism. Proteins - High molecular weight polymers of amino acids - Used for building and repairing tissues as well as for other functions Amino acids - Building blocks of proteins - End products of protein digestion Not stored in the body, leading to the constant turnover of protein. Protein turnover the continuous degradation and resynthesis of all cellular proteins. Each day, humans turnover 1-2% of their total body protein, principally muscle protein. Of the liberated amino acids, 75-80% are reutilized for new protein synthesis. The nitrogen of the remaining 20-25% forms urea. The carbon skeletons are then degraded to amphibolic intermediates.

Body proteins
Protein degradation Reutilization for new protein synthesis

Amino acids

Catabolism
Protein and amino acid turnover Because of their size (large molecules), they cannot be absorbed simply by ordinary dialysis. May be catabolized: a. Its amino group may be removed as a molecule of ammonia (oxidative deamination). b. Its amino group may be transferred to a different molecule to make a new amino acid (transamination). c. It may be degraded to carbon dioxide and water or to other non nitrogenous compounds the body can use. d. Certain amino acids can be used to make carbohydrate and lipid material in the body.

Functions/Uses 1. Protein synthesis synthesize tissue proteins either to make new tissue or to repair old ones. 2. Synthesis of nonprotein compounds that contain nitrogen e.g. nucleic acids, heme, creatine. 3. Energy production as biological fuels.

Nitrogen pool - Consists of all amino acids wherever they are found in the body (e.g. bloodstream, intercellular and extracellular fluids) and other simple nitrogenous substances. - Grand mixture of amino acids available in the cell derived from dietary sources or the degradation of protein.

Nitrogenous compounds and other nonprotein anabolic products e.g. glycogen, lipid, nucleic acid, hormones, creatine, heme

Dietary amino acids

Nitrogen pool

Tissue proteins and proteins serving special functions e.g. enzymes, hormones, antibodies, plasma proteins

Catabolic products (CO2, H2O, urea, energy)

The nitrogen pool

Nitrogen balance - The difference between total nitrogen intake and total nitrogen loss in feces, urine and perspiration. a. Positive nitrogen balance ingestion of more nitrogen than is excreted; characterizes protein formation (in growing infants and pregnant women). b. Negative nitrogen balance nitrogen output exceeds intake; indication of tissue destruction (following surgery, in advanced cancer, and following failure to ingest adequate or sufficiently high quality protein (kwashiorkor and marasmus). c. Nitrogen equilibrium nitrogen intake matches output. Reactions 1. Oxidative deamination nitrogen (the amino group) is removed from an amino acid and is converted to ammonia (NH3) when there is too much protein intake. Enzyme = [amino acid] oxidase Coenzyme = NAD, FAD

e.g. deamination of glutamic acid Ammonia is toxic to humans, therefore, it goes to the urea cycle. The keto acid may enter into a variety of metabolic routes, depending on the nature of its Rgroup.

2. Decarboxylation loss of the elements of CO2 from the carboxylic acid group in an amino acid to generate an amine. Enzyme = decarboxylase e.g. decarboxylation of lysine These amines are used by the body to synthesize nonprotein, nitrogenous compounds e.g. certain hormones and nucleic acids.

3. Transamination transfer of an amino group from an amino acid to an alpha keto acid, forming a new amino acid and a new alpha keto acid. Enzyme = transaminase e.g. transamination of alanine Shows how the body can manufacture certain amino acids from carbon skeletons of a nonprotein origin. A reversible reaction

Synthesis of urea - Urea = the major end product of nitrogen metabolism in human beings. - 30g of urea is excreted in 24 hours in healthy individuals. - It is synthesized chiefly in the liver, then it travels through the bloodstream to the kidneys, which remove it in the urine. - It is formed by the union of CO2 and NH3 in a cyclic process (Krebs ornithine cycle)

The Krebs Cycle

Or simply, 2NH3 + CO2 NH2 CO NH2 + H2O Hemoglobin - The protein of blood that carries oxygen from the lungs to other parts of the body. a. Globin a simple protein b. Heme a nonprotein molecule whose deep red color is responsible for the characteristic color of blood. - capable of holding molecules of oxygen. - manufactured by cells in the bone marrow and incorporated into erythrocytes, the red blood cells. - derived from the basic compound porphin.

Porphin

Heme

 Heme catabolism Hemoglobin Verdohemoglobin Biliverdin + Iron + Globin

Bilirubin

Plasma

Nitrogen Pool

Liver 1. 2. 3. 4. 5. 6.

Ferritin

One of the carbon bridges in the tetrapyrrole ring is removed to open the ring. Hemoglobin is now called verdohemoglobin, a slightly broken hemoglobin molecule. Verdohemoglobin splits into globin, ferrous iron, and bilirubin, the greenish tetrapyrrole pigment. Globin enters the nitrogen pool. Iron is conserved by the body in the form of a storage protein (ferritin) and is reused. Biliverdin is converted by enzymes in the liver to bilirubin.

Bilirubin A reddish orange tetrapyrrole pigment - The principal bile pigment in human beings. Bilirubin Mesobilirubinogen Bilinogen

Stercobilinogen (in feces)

Urobilinogen (in urine) Bilin (reoxidized bilinogen)

Stercobilin

Urobilin

Elimination of hemoglobin- breakdown products Bilirubin clearance test = a much used clinical test for general liver function.

Other enzymes Enzyme Pepsin Trypsin Chymotrypsin Carboxypeptidase Aminopeptidase Tripeptidase Source Gastric juice Pancreatic juice Pancreatic juice Pancreatic juice Intestinal mucosa Intestinal mucosa

Dipeptidase

Intestinal mucosa

Enzymes present in the gastrointestinal tract which are concerned with protein digestion The action of these proteolytic enzymes converts dietary protein to free amino acids which are absorbed chiefly in the small intestine.

Disorders associated with Protein metabolism 1. Hepatic coma - loss of consciousness due to liver failure. Liver failure occurs because the liver tissue has been irreversibly and progressively destroyed (cirrhosis) as a result of infection, poison, or other disease. 2. Cirrhosis the liver is not able to remove bilirubin and it remains in the circulation. Stools are clay-colored, because the tetrapyrrole pigments do not reach the intestinal tract. 3. Hemolytic jaundice bile pigments, particularly bilirubin, form faster than the liver can clear them. 4. Hepatic encephalopathy - the brain is poisoned by the toxic elements from the liver, which is no longer capable of properly filtering the blood to remove toxins. 5. Kwashiorkor - a form of malnutrition that occurs when there is not enough protein in the diet.