Catabolism of Amino Acids

Overview

Amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids (AAs) follow 3 main metabolic pathways for their metabolism:

1. Synthesis Synthesis Polymerase Chain Reaction (PCR) of new proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
2. Formation of amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids derivatives
3. Catabolism of AAs:
   • Catabolism consists of the breakdown of complex molecules into smaller units to produce energy or to be used in anabolic reactions.
   • Removal or exchange of functional groups:
     • Involves transamination, deamination, and decarboxylation
     • Releases excess nitrogen Nitrogen An element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. Urea Cycle in the form of ammonium (NH4⁺), which then enters the urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle cycle, is converted into urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle, and excreted through the urine
   • Catabolism of the remaining carbon skeleton:
     • In general, all 20 AAs can be broken down into 1 of 6 intermediates: pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis, acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle, oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle, alpha-ketoglutarate, succinyl-CoA Succinyl-CoA Citric Acid Cycle, or fumarate Fumarate Citric Acid Cycle.
     • Ketogenic AAs metabolize to acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle, later used in the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle, ketogenesis Ketogenesis Ketone Body Metabolism, or fatty acid synthesis Synthesis Polymerase Chain Reaction (PCR).
     • Glucogenic AAs are converted into glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance through gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis.
     • Some AAs are both glucogenic and ketogenic.

Amino Acid Derivatives

Amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids can be used to assemble many substances. The image below shows the most important AA-derived substances in humans.

Transamination

Transamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA AA Amyloidosis with an alpha-keto group (=O) instead of an alpha-amino group (NH₂).

• The original AA AA Amyloidosis loses an amino group and gains a keto group, becoming an alpha-keto acid.
• The original alpha-keto acid loses its keto group and gains an amino, becoming a nonessential AA AA Amyloidosis.
• The reaction is catalyzed by aminotransferase enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes:
  • Can be specific for a particular AA AA Amyloidosis pair or a group with similar chemical compositions
  • Requires coenzyme pyridoxal phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes (PLP, the active form of vitamin B6 Vitamin B6 Vitamin B 6 refers to several picolines (especially pyridoxine; pyridoxal; & pyridoxamine) that are efficiently converted by the body to pyridoxal phosphate which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, and aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate. Although pyridoxine and vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading. Most of vitamin b6 is eventually degraded to pyridoxic acid and excreted in the urine. Water-soluble Vitamins and their Deficiencies)
  • Found in high concentrations in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy

This process is need-dependent. If there is an excess of a type of AA AA Amyloidosis, the amino group of that type can be transferred to make other types of AAs that the body currently needs.

All of the common AAs participate in transamination, except lysine, threonine, proline Proline A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. Synthesis of Nonessential Amino Acids, and hydroxyproline, which catabolize via a dehydrogenase.

Transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis

• Alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids transaminase ( ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests or ALAT) transfers an amino group from alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids to alpha-ketoglutarate, forming pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis and glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids. 
• Aspartate Aspartate One of the non-essential amino acids commonly occurring in the l-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. Synthesis of Nonessential Amino Acids transaminase ( AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests or ASAT) transfers an amino group from aspartate Aspartate One of the non-essential amino acids commonly occurring in the l-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. Synthesis of Nonessential Amino Acids to alpha-ketoglutarate, forming oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle and glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids.  

Both enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes catabolize reversible reactions, which are essential for the transport of nitrogen Nitrogen An element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. Urea Cycle from tissues to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and into the urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle cycle.

Steps:

1. PLP reacts with the amino group of the AA AA Amyloidosis, releasing H₂O.
2. A Schiff base is formed, destabilizing the AA AA Amyloidosis.
3. Hydrogen atoms migrate, double-bond shifts, and aldimine → ketimine.
4. H₂O is added, yielding PMP and an alpha-keto acid.
5. In reverse, PMP reacts with an alpha-keto acid, generating an AA AA Amyloidosis and reconstituting PLP.

Deamination

Deamination is the process through which amino groups are stripped from AAs, releasing free cytotoxic Cytotoxic Parvovirus B19 ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance: ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance → ammonium → urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle or uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis via the urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle cycle in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy.

Three types of deamination

1. Oxidative deamination:

• Oxidation turns the amino group into an imino group.
• NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway⁺ or NADP⁺ is reduced to NADH/H or NADPH NADPH Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5′-phosphate (nmn) coupled by pyrophosphate linkage to the 5′-phosphate adenosine 2. Pentose Phosphate Pathway/H, respectively.
• Water is added to the amino group, converting it to an alpha-keto group, releasing ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance.

2. Hydrolytic deamination:

Water reacts with the amino group, irreversibly attaching an OH group and eliminating the amino group in the form of ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance.

3. Eliminative deamination: 

• Small AAs ( serine Serine A non-essential amino acid occurring in natural form as the l-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines; pyrimidines; and other amino acids. Synthesis of Nonessential Amino Acids or cysteine Cysteine A thiol-containing non-essential amino acid that is oxidized to form cystine. Synthesis of Nonessential Amino Acids) release water (or hydrogen sulfide Hydrogen sulfide A flammable, poisonous gas with a characteristic odor of rotten eggs. It is used in the manufacture of chemicals, in metallurgy, and as an analytical reagent. Salmonella for sulfurous amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids).
  • PLP is a necessary coenzyme.
• Through hydrolysis Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water. Proteins and Peptides, the amino group is cleaved, resulting in pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis.

Decarboxylation

• Cleavage of a carboxyl group from an AA AA Amyloidosis, releasing CO₂
• Catalyzed by the enzyme decarboxylase 
• Uses PLP as a coenzyme
• Resulting amines fulfill important functions in the body = biogenic amines
  • Histamine is formed through decarboxylation from histidine, and plays a vital role in immediate hypersensitivity reactions. 
  • Other examples:
    • Gamma-aminobutyric acid from glutamine Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. Synthesis of Nonessential Amino Acids acid
    • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS from 3,4-dihydroxyphenylalanine

Catabolism of the Carbon Skeleton

The catabolism of AAs involves anaplerotic reactions (chemical reactions that form intermediates of metabolic pathways).

The breakdown of the carbon skeleton of AAs can be classified by the metabolic pathways to which their catabolic products will serve as intermediates: 

• Glucogenic AAs → gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis intermediates
• Ketogenic AAs → ketogenesis Ketogenesis Ketone Body Metabolism intermediates
• Glucogenic and ketogenic AAs → both pathways

All AAs are broken down into 1 of 6 intermediates (see green boxes in the images below): pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis, acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle, oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle, alpha-ketoglutarate, succinyl-CoA Succinyl-CoA Citric Acid Cycle, or fumarate Fumarate Citric Acid Cycle.

Glucogenic AAs

Metabolized to pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis or metabolites of the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle (CAC):

• Pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis (from serine Serine A non-essential amino acid occurring in natural form as the l-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines; pyrimidines; and other amino acids. Synthesis of Nonessential Amino Acids, cysteine Cysteine A thiol-containing non-essential amino acid that is oxidized to form cystine. Synthesis of Nonessential Amino Acids, glycine Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Synthesis of Nonessential Amino Acids, alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids, and threonine)
• Succinyl-CoA Succinyl-CoA Citric Acid Cycle (from methionine, isoleucine, valine, and threonine via propionyl-Coa and methylmalonyl-CoA Methylmalonyl-CoA Fatty Acid Metabolism
• Propionyl-CoA (intermediate of succinyl-CoA Succinyl-CoA Citric Acid Cycle pathway)
• Oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle (from asparagine Asparagine A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from aspartic acid and ammonia by asparagine synthetase. Synthesis of Nonessential Amino Acids via aspartate Aspartate One of the non-essential amino acids commonly occurring in the l-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. Synthesis of Nonessential Amino Acids)
• α-Ketoglutarate (from glutamine Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. Synthesis of Nonessential Amino Acids, arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle, histidine, proline Proline A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. Synthesis of Nonessential Amino Acids via glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids)
• Fumarate Fumarate Citric Acid Cycle

Catabolic products either move into the CAC to produce energy or are used as substrates for gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis.

Ketogenic AAs

Metabolized directly to acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle, then enter 1 of 3 metabolic pathways:

• Enter the CAC to produce ATP/energy
• Ketogenesis Ketogenesis Ketone Body Metabolism (production of ketone bodies Ketone bodies The metabolic substances acetone; 3-hydroxybutyric acid; and acetoacetic acid (acetoacetates). They are produced in the liver and kidney during fatty acids oxidation and used as a source of energy by the heart, muscle and brain. Ketone Body Metabolism)
• Synthesis Synthesis Polymerase Chain Reaction (PCR) of fatty acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance or cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism

Glucogenic and Ketogenic AAs

Metabolized to intermediates of lipidic as well as glucogenic pathways:

• Isoleucine → propionyl-CoA (→ methylmalonyl-CoA Methylmalonyl-CoA Fatty Acid Metabolism → succinyl-CoA Succinyl-CoA Citric Acid Cycle) and acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle
• Phenylalanine Phenylalanine An essential aromatic amino acid that is a precursor of melanin; dopamine; noradrenalin (norepinephrine), and thyroxine. Synthesis of Nonessential Amino Acids → tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids → fumarate Fumarate Citric Acid Cycle and acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle
• Threonine → propionyl-CoA and pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis as well as acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle (via glycine Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Synthesis of Nonessential Amino Acids + acetaldehyde Acetaldehyde A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. Ethanol Metabolism)
• Tryptophan → alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids and acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle

Mnemonic

To recall the metabolic pathways of the carbon skeletons of amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids, remember:

• Glucogenic: “I Met MET Preoperative CareHisValentine, she is so sweet.”
  • Met MET Preoperative Carehionine
  • Histidine
  • Valine
• Ketogenic: “The onLy pureLy ketogenic amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids.”
  • Leucine
  • Lysine

Clinical Relevance

The following conditions are disorders of amino acid metabolism Disorders of amino acid metabolism Amino acids are the building blocks of proteins, whose production is a tightly regulated enzymatic cascade. Disorders of the enzymes involved in amino acid metabolism are often serious and present early in life. Congenital errors in amino acid metabolism are due to either impaired synthesis or degradation. Disorders of Amino Acid Metabolism. Depending on the country and the individual U.S. state, newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn infants may be routinely screened for these disorders (except for alkaptonuria).

• Phenylketonuria: a defect of phenylalanine hydroxylase Phenylalanine hydroxylase An enzyme of the oxidoreductase class that catalyzes the formation of l-tyrosine, dihydrobiopterin, and water from l-phenylalanine, tetrahydrobiopterin, and oxygen. Synthesis of Nonessential Amino Acids that results in the impairment of the conversion of phenylalanine Phenylalanine An essential aromatic amino acid that is a precursor of melanin; dopamine; noradrenalin (norepinephrine), and thyroxine. Synthesis of Nonessential Amino Acids to tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids and subsequent accumulation of phenylalanine Phenylalanine An essential aromatic amino acid that is a precursor of melanin; dopamine; noradrenalin (norepinephrine), and thyroxine. Synthesis of Nonessential Amino Acids. Presents as psychomotor delay and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
• Maple syrup urine disease Maple syrup urine disease An autosomal recessive inherited disorder with multiple forms of phenotypic expression, caused by a defect in the oxidative decarboxylation of branched-chain amino acids. These metabolites accumulate in body fluids and render a ‘maple syrup’ odor. The disease is divided into classic, intermediate, intermittent, and thiamine responsive subtypes. The classic form presents in the first week of life with ketoacidosis, hypoglycemia, emesis, neonatal seizures, and hypertonia. The intermediate and intermittent forms present in childhood or later with acute episodes of ataxia and vomiting. Disorders of Amino Acid Metabolism: a defect in dehydrogenase that results in the accumulation of branched-chain AAs. Presents as cognitive disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment, sweet-smelling urine, and dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia 
• Homocystinuria: a defect in the enzyme cystathionine β-synthase, which leads to an accumulation of homocysteine. Presents as flushing, developmental delay, lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy dislocation, vascular disease, and osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
• Tyrosinemia Tyrosinemia A group of disorders which have in common elevations of tyrosine in the blood and urine secondary to an enzyme deficiency. Type I tyrosinemia features episodic weakness, self-mutilation, hepatic necrosis, renal tubular injury, and seizures and is caused by a deficiency of the enzyme fumarylacetoacetase. Type II tyrosinemia features intellectual disability, painful corneal ulcers, and keratosis of the palms and plantar surfaces and is caused by a deficiency of the enzyme tyrosine transaminase. Type III tyrosinemia features intellectual disability and is caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase. Renal Tubular Acidosis: a deficiency of fumarylacetoacetate hydrolase, the last enzyme in the tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids catabolism. Presents as liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease, deficient weight gain, peripheral nerve disease, and kidney defects
• Alkaptonuria: a deficiency of homogentisic acid dioxygenase, which impairs the normal degradation of tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids to fumarate Fumarate Citric Acid Cycle. Presents as a bluish-black discoloration of connective tissues, arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, and calcifications of various tissues.