AA Metabolism PDF

ENZYMES 1. Alanine Alanine Transaminase (ALT): Converts alanine and α-ketoglutarate to pyruvate and glutamate. Alanine Dehydrogenase: Converts alanine to pyruvate, releasing ammonia. 2. Arginine Arginase: Converts arginine to ornithine and urea in the urea cycle. Nitric Oxide Sy...

ENZYMES 1. Alanine Alanine Transaminase (ALT): Converts alanine and α-ketoglutarate to pyruvate and glutamate. Alanine Dehydrogenase: Converts alanine to pyruvate, releasing ammonia. 2. Arginine Arginase: Converts arginine to ornithine and urea in the urea cycle. Nitric Oxide Synthase (NOS): Converts arginine to nitric oxide (NO) and citrulline. Arginine Decarboxylase: Converts arginine to agmatine. 3. Asparagine Asparaginase: Converts asparagine to aspartate, releasing ammonia. Asparagine Synthetase: Converts aspartate and glutamine to asparagine. 4. Aspartate Aspartate Transaminase (AST): Converts aspartate and α-ketoglutarate to oxaloacetate and glutamate. Aspartate Deaminase: Converts aspartate to ammonia and fumarate. 5. Cysteine Cystathionine β-synthase: Converts homocysteine and serine to cystathionine. Cystathionine γ-lyase: Converts cystathionine to cysteine, producing ammonia and α- ketobutyrate. Cysteine Sulfinic Acid Decarboxylase: Converts cysteine sulfinic acid to hypotaurine. 6. Glutamate Glutamate Dehydrogenase: Converts glutamate to α-ketoglutarate, producing ammonia. Glutamine Synthetase: Converts glutamate and ammonia to glutamine. Glutamate Synthase: Converts α-ketoglutarate and glutamine to two glutamates. 7. Glutamine Glutaminase: Converts glutamine to glutamate, releasing ammonia. Glutamine Synthetase: Converts glutamate and ammonia to glutamine. 8. Glycine Glycine Cleavage System: Converts glycine to serine, involving: o Glycine Decarboxylase: Catalyzes the decarboxylation of glycine. o Tetrahydrofolate-Dependent Glycine Cleavage Enzyme: Transfers carbon from glycine to tetrahydrofolate. 9. Histidine Histidine Decarboxylase: Converts histidine to histamine. Histidase: Converts histidine to urocanic acid. 10. Isoleucine Isoleucine Aminotransferase: Converts isoleucine to α-ketobutyrate and glutamate. Branched-Chain Keto Acid Dehydrogenase: Converts α-ketoisovalerate to isovaleryl-CoA. 11. Leucine Leucine Aminotransferase: Converts leucine to α-ketoisocaproate and glutamate. Branched-Chain Keto Acid Dehydrogenase: Converts α-ketoisocaproate to isovaleryl- CoA. 12. Lysine Lysine Decarboxylase: Converts lysine to cadaverine. Lysine Acetyltransferase: Catalyzes the acetylation of lysine residues in proteins. 13. Methionine Methionine Adenosyltransferase: Converts methionine to S-adenosylmethionine (SAM), a key methyl donor. Cystathionine β-synthase: Converts homocysteine to cysteine. 14. Phenylalanine Phenylalanine Hydroxylase: Converts phenylalanine to tyrosine, using tetrahydrobiopterin as a cofactor. Tyrosine Aminotransferase: Converts tyrosine to p-hydroxyphenylpyruvate. 15. Proline Proline Dehydrogenase: Converts proline to Δ¹-pyrroline-5-carboxylate. Proline Oxidase: Converts proline to proline-2-carboxylate. 16. Serine Serine Hydroxymethyltransferase: Converts serine to glycine and is involved in one- carbon metabolism. Serine Deaminase: Converts serine to pyruvate and ammonia. 17. Threonine Threonine Deaminase: Converts threonine to α-ketobutyrate. Threonine Synthase: Converts homoserine to threonine. 18. Tryptophan Tryptophan 2,3-Dioxygenase: Converts tryptophan to kynurenine in the first step of tryptophan catabolism. Tryptophan Hydroxylase: Converts tryptophan to 5-hydroxytryptophan (5-HTP), a precursor for serotonin. 19. Tyrosine Tyrosine Aminotransferase: Converts tyrosine to p-hydroxyphenylpyruvate. Tyrosine Hydroxylase: Converts tyrosine to L-DOPA, a precursor for dopamine. 20. Valine Valine Aminotransferase: Converts valine to α-ketoisovalerate and glutamate. Branched-Chain Keto Acid Dehydrogenase: Converts α-ketoisovalerate to isovaleryl-CoA. PRODUCTS 1. Phenylalanine Primary Product: Tyrosine (via phenylalanine hydroxylase). Further Metabolism of Tyrosine: o Catecholamines: Tyrosine is converted to dopamine, norepinephrine, and epinephrine, which are crucial neurotransmitters. o Melanin: Tyrosine is a precursor for melanin production through the enzyme tyrosinase. o Fumarate and Acetoacetate: In the breakdown of tyrosine, fumarate (gluconeogenic) and acetoacetate (ketogenic) are produced. This dual outcome makes tyrosine both glucogenic and ketogenic. 2. Tyrosine o Dopamine, Norepinephrine, and Epinephrine: Through a series of hydroxylation and decarboxylation reactions, tyrosine forms catecholamines, essential for brain function and stress response. o Melanin: In melanocytes, tyrosine is converted into melanin, a pigment that protects the skin from UV radiation. o Fumarate and Acetoacetate: These intermediates are generated as tyrosine undergoes breakdown, which can be used in the Krebs cycle (fumarate) or ketone body production (acetoacetate). 3. Tryptophan o Serotonin: Tryptophan is converted to serotonin, a neurotransmitter important for mood and sleep regulation. o Melatonin: Serotonin can be further metabolized into melatonin, a hormone involved in circadian rhythms. o Nicotinamide (Vitamin B3): Through the kynurenine pathway, tryptophan is metabolized to form nicotinamide, a precursor of NAD+ (nicotinamide adenine dinucleotide), essential for cellular energy. o Acetyl-CoA and Pyruvate: Tryptophan catabolism can yield acetyl-CoA and pyruvate, which contribute to energy production. 4. Histidine o Glutamate: Histidine is converted to glutamate via urocanic acid and FIGLU (formiminoglutamate) as intermediates. o Histamine: Through decarboxylation, histidine forms histamine, a mediator in immune responses, allergies, and gastric acid secretion. 5. Valine o Succinyl-CoA: Valine is catabolized to succinyl-CoA, a Krebs cycle intermediate, making it a glucogenic amino acid. o Methylmalonic Acid: One of the intermediate steps in valine catabolism, where accumulation (due to vitamin B12 deficiency) can cause methylmalonic acidemia. 6. Leucine o Acetyl-CoA and Acetoacetate: Leucine undergoes breakdown to yield acetyl-CoA and acetoacetate, making it a strictly ketogenic amino acid used in ketone body formation. o HMG-CoA (3-Hydroxy-3-Methylglutaryl-CoA): Leucine’s breakdown produces HMG-CoA, an intermediate also involved in cholesterol synthesis. 7. Isoleucine o Acetyl-CoA and Succinyl-CoA: Isoleucine metabolism produces both acetyl-CoA (ketogenic) and succinyl-CoA (glucogenic), thus making it both ketogenic and glucogenic. 8. Methionine o Homocysteine: Methionine is first converted to S-adenosylmethionine (SAM), a major methyl donor, which then forms homocysteine. o Cysteine: Homocysteine can convert to cysteine via the transsulfuration pathway, with the enzyme cystathionine synthase. o S-Adenosylmethionine (SAM): This molecule, derived from methionine, donates methyl groups in various reactions essential for DNA methylation and neurotransmitter synthesis. 9. Cysteine o Pyruvate: Cysteine is ultimately broken down into pyruvate through the cysteine sulfinate pathway. o Taurine: Cysteine can also convert to taurine, a compound that conjugates bile acids and is involved in antioxidant functions. o Sulfate: Through oxidation, cysteine produces sulfate, which is important for detoxification and structural proteins. 10. Lysine o Acetoacetyl-CoA: Lysine is metabolized to acetoacetyl-CoA, making it a ketogenic amino acid. o Carnitine: Lysine, along with methionine, is a precursor for carnitine, which is essential for the transport of fatty acids into mitochondria for β-oxidation. 11. Arginine o Urea: Arginine is converted to urea in the final step of the urea cycle.  o Ornithine: As arginine is broken down to produce urea, ornithine is regenerated and re-enters the urea cycle. o Nitric Oxide (NO): Arginine is the precursor for nitric oxide, a vasodilator involved in blood pressure regulation and neurotransmission. o Creatine: Along with glycine, arginine helps form creatine, which provides quick energy to muscle cells. 12. Ornithine o Citrulline: Ornithine combines with carbamoyl phosphate to form citrulline in the urea cycle. o Polyamines (Spermidine and Spermine): Ornithine decarboxylation produces polyamines, which are essential for cell growth and stability. 13. Aspartate o Oxaloacetate: Aspartate is converted to oxaloacetate, a key Krebs cycle intermediate, making it a glucogenic amino acid. o Urea Cycle Intermediate: Aspartate provides the second nitrogen in the urea cycle by combining with citrulline to form argininosuccinate. 14. Glutamate o α-Ketoglutarate: Glutamate dehydrogenase converts glutamate to α- ketoglutarate, which enters the Krebs cycle. o GABA (Gamma-Aminobutyric Acid): By decarboxylation, glutamate forms GABA, an inhibitory neurotransmitter crucial for reducing neuronal excitability. 15. Glutamine o Glutamate: Glutamine is hydrolyzed to glutamate, releasing ammonia, which is then excreted via the urea cycle. o Nitrogen Donor: Glutamine provides nitrogen for various biosynthetic reactions, such as purine and pyrimidine synthesis. 16. Alanine o Pyruvate: Alanine is converted to pyruvate via transamination, which can then be used in gluconeogenesis. 17. Glycine o Serine: Glycine is converted to serine via a hydroxymethyl group transfer. o Heme: Glycine is a precursor in the synthesis of heme, an essential component of hemoglobin. o Creatine: Glycine combines with arginine and methionine to form creatine. o Purines: Glycine contributes to the formation of purines, which are essential for DNA and RNA synthesis. 18. Proline o Glutamate: Proline is converted to glutamate via oxidation and transamination.  o Collagen Synthesis: Proline is hydroxylated to hydroxyproline, a crucial component of collagen, providing structural stability in connective tissues. 19. Serine o Pyruvate: Serine is deaminated to form pyruvate, which can enter gluconeogenesis. o Glycine: Serine can be converted to glycine through serine hydroxymethyltransferase, which also produces a one-carbon group for folate metabolism. 20. Threonine o Succinyl-CoA: Threonine can be broken down to succinyl-CoA, entering the Krebs cycle as a glucogenic intermediate. o Glycine and Acetaldehyde: Threonine cleavage yields glycine and acetaldehyde, contributing to one-carbon metabolism. DISEASES 1. Phenylketonuria (PKU) Amino Acid: Phenylalanine Description: Caused by a deficiency in phenylalanine hydroxylase, leading to an accumulation of phenylalanine and associated with intellectual disability if untreated. 2. Tyrosinemia Amino Acid: Tyrosine Types: o Type I (Hepatorenal Tyrosinemia): Due to deficiency in fumarylacetoacetate hydrolase, causing liver failure and renal dysfunction. o Type II (Oculocutaneous Tyrosinemia): Results from tyrosine aminotransferase deficiency, leading to skin and eye lesions. Other Names: Type II is also called Richner-Hanhart Syndrome. 3. Maple Syrup Urine Disease (MSUD) Amino Acids: Valine, Leucine, and Isoleucine (Branched-Chain Amino Acids) Description: Caused by a deficiency in branched-chain α-keto acid dehydrogenase, leading to toxic levels of branched-chain keto acids. Urine has a characteristic sweet odor. 4. Hartnup Disease Amino Acid: Tryptophan Description: Caused by defective tryptophan transport in the intestines and kidneys, leading to symptoms similar to pellagra due to niacin deficiency. 5. Carcinoid Syndrome Amino Acid: Tryptophan Description: Linked to tumors that secrete serotonin and other hormones, often diagnosed by elevated levels of 5-Hydroxyindoleacetic Acid (5-HIAA) in urine. 6. Blue Diaper Syndrome Amino Acid: Tryptophan Description: Caused by impaired tryptophan absorption, characterized by hypercalcemia, nephrocalcinosis, and indicanuria (blue-colored urine). 7. Histidinemia Amino Acid: Histidine Description: Caused by a deficiency in histidase, leading to elevated levels of histidine in the blood. 8. Homocystinuria Amino Acid: Methionine Description: Caused by a deficiency in cystathionine β-synthase, leading to high levels of homocysteine, which can cause cardiovascular and skeletal problems. 9. Cystinuria Amino Acids: Cystine, Lysine, Arginine, and Ornithine Description: A renal transport defect affecting the reabsorption of these amino acids, leading to cystine kidney stones. 10. Cystinosis Amino Acid: Cystine Description: A lysosomal storage disease due to impaired transport of cystine out of lysosomes, leading to cystine crystal accumulation in various tissues and renal failure. 11. Alkaptonuria Amino Acid: Tyrosine Description: Caused by a deficiency in homogentisate oxidase, leading to accumulation of homogentisic acid, which causes dark urine and can lead to joint issues over time. 12. Hyperammonemia Types I and II Amino Acids: Ornithine (Type I) and Glutamine (Type II) Description: o Type I: Due to a deficiency in carbamoyl phosphate synthetase. o Type II: Caused by a deficiency in ornithine transcarbamylase, both leading to high levels of ammonia in the blood, which is neurotoxic. 13. Citrullinemia Amino Acid: Citrulline Description: Caused by a deficiency in argininosuccinate synthetase, leading to citrulline accumulation and hyperammonemia. 14. Argininosuccinic Aciduria Amino Acid: Arginine Description: Caused by a deficiency in argininosuccinate lyase, leading to accumulation of argininosuccinic acid and ammonia, causing neurological symptoms. 15. Argininemia Amino Acid: Arginine Description: Caused by a deficiency in arginase, leading to arginine accumulation and hyperammonemia, causing growth delay and neurological symptoms. QUESTIONS 1. What is protein turnover, and how much body protein is turned over daily? Protein turnover is the continuous breakdown and synthesis of proteins, with approximately 1-2% of body protein turned over each day. 2. Which enzymes are involved in intracellular protein degradation? Intracellular protein degradation involves two main systems: 3. Ubiquitin-proteasome (ATP-dependent) degrades proteins tagged for destruction. Lysosomal degradation (ATP-independent) uses acid hydrolases for long-lived or damaged proteins. 4. Describe the role of the liver in amino acid metabolism. The liver is central to amino acid metabolism, involved in synthesizing non-essential amino acids, delivering amino acids to other organs, and processing nitrogen for excretion through the urea cycle. 5. What are glucogenic amino acids, and can you give examples? Glucogenic amino acids are used to generate glucose via gluconeogenesis. Examples include alanine, asparagine, glutamine, methionine, serine, threonine, and valine. 6. Which amino acids are exclusively ketogenic? Ketogenic amino acids, such as leucine and lysine, are used to produce ketone bodies, particularly during fasting or low-carb diets. 7. What is the fate of amino acids in a negative nitrogen balance? Negative nitrogen balance occurs under metabolic stress, essential amino acid deficiency, or malnutrition, resulting in more nitrogen being excreted than consumed. 8. How does the body handle excess ammonia produced by amino acid metabolism? The liver detoxifies ammonia by converting it to urea through the urea cycle, which is then excreted in the urine. 9. Explain the role of carbamoyl phosphate synthetase in the urea cycle. Carbamoyl phosphate synthetase I initiates the urea cycle by forming carbamoyl phosphate from ammonia, which is a crucial nitrogen donor in the process. 10. Describe the impact of hyperammonemia on the body. Hyperammonemia causes toxic levels of ammonia in the bloodstream, leading to neurotoxicity, which can result in brain damage or coma if untreated. 11. What is the function of the enzyme argininosuccinate synthetase? Argininosuccinate synthetase catalyzes the formation of argininosuccinate from citrulline and aspartate, an essential step in the urea cycle. 12. How is protein digestion initiated in the stomach? Protein digestion begins in the stomach with the activation of pepsinogen to pepsin, which breaks down proteins into smaller peptides. 13. Name the enzymes secreted by the pancreas for protein digestion. The pancreas secretes trypsin, chymotrypsin, carboxypeptidase, and elastase, which further break down proteins in the small intestine. 14. Explain how amino acids are absorbed in the small intestine. Amino acids are absorbed via Na+-dependent active transport, facilitated diffusion, and the gamma-glutamyl cycle. 15. What is the Glucose-Alanine Cycle and its significance? The Glucose-Alanine Cycle transports nitrogen from muscles to the liver for urea synthesis and provides glucose for muscle energy, helping regulate blood glucose levels. 16. What role does phenylalanine hydroxylase play in amino acid metabolism? Phenylalanine hydroxylase converts phenylalanine to tyrosine, a crucial step for normal metabolic function and neurotransmitter synthesis. 17. Explain the defect in phenylketonuria (PKU) and its effects. PKU is caused by a deficiency in phenylalanine hydroxylase, leading to toxic accumulation of phenylalanine, which can result in developmental delays and intellectual disability if untreated. 18. Describe the key steps in the breakdown of tryptophan. Tryptophan is metabolized to serotonin, melatonin, and nicotinamide (a vitamin B3 precursor) via pathways involving serotonin synthesis or the kynurenine pathway. 19. How is serotonin synthesized from tryptophan? Tryptophan is converted to 5-hydroxytryptophan via tryptophan hydroxylase, then decarboxylated to form serotonin. 20. What enzyme deficiency causes maple syrup urine disease? Maple syrup urine disease is caused by a deficiency in branched-chain α-keto acid dehydrogenase, leading to an accumulation of branched-chain keto acids. 21. Explain the biochemical basis of Hartnup disease. Hartnup disease is due to a defective tryptophan transporter in the kidneys and intestine, causing decreased tryptophan absorption and niacin deficiency, leading to pellagra-like symptoms. 22. What causes tyrosinemia and what are its types?  Tyrosinemia is caused by enzyme deficiencies in tyrosine metabolism, leading to toxic metabolite accumulation. Type I affects the liver and kidneys, while Type II results in eye and skin problems. 23. How is melatonin synthesized from tryptophan? Tryptophan is first converted to serotonin, which is then acetylated and methylated to form melatonin in the pineal gland. 24. What are the functions of melatonin in the body? Melatonin regulates the sleep-wake cycle, with synthesis peaking at night to promote sleep. 25. Explain the formation of homocysteine from methionine. Methionine is converted to homocysteine through a series of reactions involving S- adenosylmethionine and S-adenosylhomocysteine as intermediates. 26. Describe the two main pathways of cysteine catabolism. Cysteine is catabolized either through the cysteine sulfinate pathway, leading to pyruvate production, or the transamination pathway. 27. What is cystinuria and its primary symptom? Cystinuria is a defect in the transport of cystine in the kidneys, causing kidney stones due to cystine accumulation. 28. Describe the conversion of histidine to glutamate. Histidine is converted to glutamate via the intermediates urocanic acid and FIGLU, with FIGLU used in diagnostic tests for folate deficiency. 29. What is the Figlu test used for? The FIGLU test is used to assess folate levels, as increased FIGLU excretion suggests folic acid deficiency. 30. Explain the significance of the enzyme glutamine synthetase. Glutamine synthetase catalyzes the conversion of glutamate to glutamine by incorporating ammonia, aiding in ammonia detoxification. 31. How does the body detoxify ammonia by asparagine formation? Asparagine synthetase catalyzes aspartate + NH3 → asparagine, which helps remove ammonia. 32. What inborn error leads to hyperammonemia type I? Hyperammonemia Type I results from carbamoyl phosphate synthetase I deficiency, leading to ammonia buildup. 33. Describe the therapy for treating urea cycle enzyme deficiencies. Treatment includes protein restriction, ammonia-binding compounds (e.g., sodium benzoate), and supplementation with intermediates like arginine. 34. Explain the function of lactulose in ammonia intoxication. Lactulose acidifies the colon, converting ammonia to non-absorbable ammonium, which is then excreted. 35. What is the role of dietary benzoate in urea cycle disorders? Sodium benzoate binds glycine to form hippurate, which is excreted, helping reduce ammonia levels. 36. Describe the steps of arginine synthesis in the urea cycle. Arginine is formed from argininosuccinate, which splits into fumarate and arginine. Arginase then converts arginine into urea and regenerates ornithine. 37. How is citrulline converted to argininosuccinate? Citrulline combines with aspartate, catalyzed by argininosuccinate synthetase, to form argininosuccinate. 38. What is the function of ornithine transcarbamylase? Ornithine transcarbamylase combines ornithine and carbamoyl phosphate to produce citrulline in the urea cycle. 39. Describe the defect in citrullinemia and its consequences. Citrullinemia is caused by a deficiency in argininosuccinate synthetase, leading to citrulline accumulation and hyperammonemia. 40. Explain the regulatory role of the Glucose-Alanine Cycle. The Glucose-Alanine Cycle transports nitrogen to the liver, helping prevent toxic ammonia buildup in muscles and maintaining blood glucose levels. 41. What enzyme catalyzes the reversible conversion of glutamate and α-ketoglutarate? Glutamate dehydrogenase converts glutamate to α-ketoglutarate and ammonia, balancing nitrogen levels. 42. Explain the role of α-keto acids in amino acid metabolism. α-Keto acids can enter the Krebs cycle or be used in gluconeogenesis for energy production. 43. What are the metabolic fates of leucine? Leucine is ketogenic and metabolized to acetoacetate and acetyl-CoA. 44. What compound is used to assess liver function through detoxification?  The hippuric acid test evaluates liver function, as benzoic acid binds glycine to form hippurate, which is excreted. 45. Describe the synthesis of creatine from glycine, arginine, and methionine. Glycine and arginine form guanidinoacetate, which combines with methionine to produce creatine, stored in muscles for energy. 46. How does cystinosis differ from cystinuria? Cystinosis is a storage disorder where cystine accumulates in cells, whereas cystinuria is a transport defect leading to kidney stones. 47. Describe the role of polyamines in cell proliferation. Polyamines stabilize DNA and promote cell growth, with roles in cellular signaling and structural maintenance. 48. What is the function of nitric oxide synthesized from arginine? Nitric oxide acts as a neurotransmitter, smooth muscle relaxant, and vasodilator, lowering blood pressure. 49. Explain how histamine is derived from histidine and its physiological role. Histamine is produced by decarboxylating histidine and mediates inflammation, allergic responses, and gastric acid secretion. 50. Describe the pathway from tyrosine to norepinephrine and epinephrine. Tyrosine converts to dopa, then dopamine, which is hydroxylated to norepinephrine and methylated to epinephrine. 51. What is the biochemical function of the urea cycle enzyme arginase? Arginase catalyzes the final step of the urea cycle, converting arginine to urea and regenerating ornithine.