Biochemistry - Amino Acids Metabolism PDF

Biochemistry Amino Acids Metabolism Amino Acids Metabolism Amino Acids Metabolism Kwashiorkor Marasmus It develops in children whose diets are deficient of protein It occurs in children between 6 month and 3 years of age It is due to the deficiency of proteins and calories It is common in infants un...

Biochemistry Amino Acids Metabolism Amino Acids Metabolism Amino Acids Metabolism Kwashiorkor Marasmus It develops in children whose diets are deficient of protein It occurs in children between 6 month and 3 years of age It is due to the deficiency of proteins and calories It is common in infants under 1 year of age Subcutaneous fat is preserved Subcutaneous fat is not preserved Oedema is present Oedema is absent Enlarged fatty liver No fatty lever Amino Acids Metabolism Overview: Amino acids serve as substrates for the synthesis of protein. Amino acids provide nitrogen for the synthesis of other nitrogen-containing compounds. Amino acids are catabolized as fuels. Amino Acids Metabolism Overview: Amino Acids Metabolism Classification of Amino Acids: 1. Chemical Classification: According to the chemistry of the side chains. According to polarity of side chains. 2. Nutritional Classification: Essential. Non-essential. Amino Acids Metabolism Classification of Amino Acids: Note: All of the 20 amino acids present in proteins are essential for health. Some clinical conditions are associated with amino acid deficiency states, such as Kwashiorkor and Marasmus diseases. Kwashiorkor is protein deficiency with adequate energy intake whereas Marasmus is inadequate energy intake in all forms, including protein. Amino Acids Metabolism Amino Acids Metabolism Amino Acid Requirements of Humans: Nutritionally Essential Nutritionally Nonessential Arginine Alanine Histidine Asparagine Isoleucine Aspartate Leucine Cysteine Lysine Glutamate Methionine Glutamine Phenylalanine Glycine Threonine Hydroxyproline Tryptophan Hydroxylysine Valine Proline Serine Tyrosine Amino Acids Metabolism Classification of Amino Acids: “Nutritionally semiessential.” Synthesized at rates inadequate to support growth of children. Not necessary for protein synthesis but formed during posttranslational processing of collagen. Amino Acids Metabolism Classification of Amino Acids: 3. Metabolic Classification: Ketogenic (Leucine and Lysine). Both glucogenic and ketogenic (Isoleucine, Phenylalanine, Tryptophan, Tyrosine and Threonine). Glucogenic (all the remaining). Amino Acids Metabolism Amino Acids Pool Amino Acids Pool The amount of free amino acids distributed throughout the body is called amino acid pool. Plasma level for most amino acids varies widely throughout the day. It ranges between 4–8 mg/dl. It tends to increase in the fed state and tends to decrease in the post absorptive state. Sources of Amino Acid Pool: 1. Dietary protein. 2. Breakdown of tissue proteins. 3. Biosynthesis of nonessential amino acids. Amino Acids Pool Note: In general, the rate of protein synthesis equals the rate of degradation (steadystate). However, there is a constant need for dietary intake of protein because: Some amino acids are also used for energy production and storage and for synthesis of non-protein molecules. There are situations where protein synthesis must exceed protein degradation, such as during growth, pregnancy, and recovery from illness. Amino Acids Pool Digestion of Dietary Proteins: Protein digestion begins in the stomach. The highly acidic environment of the stomach denatures proteins. Denatured proteins are susceptible to proteolytic digestion. The primary enzyme involved in proteolytic digestion is pepsin, which catalyzes the nonspecific hydrolysis of peptide bonds at an optimal pH of 2. In the lumen of the small intestine, the pancreas secretes zymogens of trypsin (Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when either is followed by proline), chymotrypsin (Chymotrypsin prefers large hydrophobic residues. Amino Acids Pool Digestion of Dietary Proteins: Amino Acids Pool Digestion of Dietary Proteins: Chymotrypsin preferentially catalyzes the hydrolysis of peptide bonds involving tyrosine, phenylalanine, and tryptophan), elastase etc. Proteolytic enzymes break the proteins down into free amino acids as well as dipeptides and tripeptides, which in turn are absorbed by the intestinal mucosa cells and subsequently are released into the blood stream where they are absorbed by other tissues. Amino Acids Pool Turnover of Cellular Proteins: Turnover of cellular proteins (continuous degradation and synthesis) occur in all forms of life. Each day, humans turn over 1% to 2% of their total body protein, principally muscle protein. Approximately 75% of the amino acids liberated by protein degradation are reutilized, the remaining excess free amino acids are not stored for future use (i.e. amino acids not immediately incorporated into new protein are rapidly degraded). The relative susceptibility of a protein to degradation is expressed as its half-life (t1/2). Half-lives of proteins may range from under 30 minutes to over 150 hours, or even the life time of an organ. Amino Acids Pool Pathways of Protein Degradation: A. General “Non-Specific” Protein Degradation: Takes place in lysosomes (specialized organelles that operate at low pH (to denature proteins) and contain proteases for proteins, lipases for lipids, and many other hydrolases (~ 50 total)). By this pathway extracellular, membrane-associated, and long-lived intracellular proteins are degraded in lysosomes by ATP-independent processes. Amino Acids Pool Pathways of Protein Degradation: A. General “Non-Specific” Protein Degradation: Many normal and pathological processes involve increased lysosomal activity, including: Disuse atrophy of muscles and regression of the uterus after childbirth (the muscular mass of the uterus is reduced from about 2 kg to about 50 g in just nine days). Chronic inflammatory diseases such as rheumatoid arthritis involve extracellular release lysosomal enzymes, which attack surrounding tissues. Amino Acids Pool Pathways of Protein Degradation: B. Controlled or Programmed Protein Degradation Involves the UbiquitinProteasome System: Degradation of regulatory proteins with short half-lives and of abnormal or misfolded proteins occurs in the cytosol within the proteasomes, and requires ATP and ubiquitin (Ub) (a small polypeptide found in all eukaryotic cells, by which the cell distinguish between functional proteins and intracellular proteins that need to be degraded). Three different enzymes add progressively more Ub molecules, in tandem chains, an energy-requiring process (ATP). The more Ub molecules attached, the more rapid the degradation. Amino Acids Pool Pathways of Protein Degradation: B. Controlled or Programmed Protein Degradation Involves the Ubiquitin-Proteasome System: Carboxyl terminal of Ub is attached to the ε-amino groups of lysyl residues in the target protein (isopeptide bond). The residue present at its amino terminus affects whether a protein is ubiquitinated. Amino terminal Met, or Ser residues retard, whereas Asp, or Arg accelerate ubiquitination. Subsequent degradation of Ub-tagged proteins takes place in the proteasome, a macromolecule that also is ubiquitous in eukaryotic cells. Amino Acids Pool Representation of the structure of a proteasome The upper ring is gated to permit only polyubiquitinated proteins to enter the proteosome, where immobilized internal proteases degrade them to peptides. Amino Acids Pool Reactions involved in the attachment of ubiquitin (Ub) to proteins Amino Acids Pool What Controls the Rate of Protein Degradation? Different proteins are degraded at different rates. Abnormal proteins are quickly degraded, whereas the rate of degradation of normal proteins may vary widely depending on their functions. Enzymes at important metabolic control points may be degraded much faster than those enzymes whose activity is largely constant under all physiological conditions. Amino Acids Pool What Controls the Rate of Protein Degradation? Degradation of normal proteins with comparable functions depends on: N-terminal residue, the residue present at its amino terminal affects whether a protein is ubiquitinated and subsequently degraded. Amino terminal Met or Ser retards whereas Asp or Arg accelerates ubiquitination. PEST sequences, regions rich in proline (P), glutamate (E), serine (S), and threonine (T), target some proteins for rapid degradation. Amino Acids Pool Interorgan Exchange of Amino Acids: The net balance between release from endogenous protein stores and utilization by various tissues keeps the steady-state concentrations of circulating plasma amino acids between meals. In the postabsorptive state, free amino acids, particularly alanine and glutamine, are released from muscle into the circulation. Alanine is extracted primarily by the liver, and glutamine is extracted by the gut and the kidney, both of which convert a significant portion to alanine. Alanine is a key gluconeogenic amino acid, and the rate of hepatic gluconeogenesis from alanine is far higher than from all other amino acids. Amino Acids Pool Interorgan Exchange of Amino Acids: Glutamine also serves as a source of ammonia for excretion by the kidney. Branched-chain amino acids, particularly valine, are released by muscle and taken up predominantly by the brain. The kidney provides a major source of serine for uptake by peripheral tissues, including liver and muscle. In the fed state (following a protein-rich meal), the splanchnic tissues release amino acids while the peripheral muscles extract amino acids Amino Acids Pool Interorgan amino acid exchange in normal postabsorptive humans