The catabolism of amino acidsAmino acidsOrganic 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 results in the release of nitrogen in the form of ammonium. This excess nitrogen is transported to the liverLiverThe 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 kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy and eliminated from the body in the form of urea via the urine. The urea cycle (or ornithine cycle) takes place mainly in the liverLiverThe 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 comprises the synthesisSynthesisPolymerase Chain Reaction (PCR) of urea from ammonium, CO2, aspartateAspartateOne 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, and bicarbonateBicarbonateInorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.Electrolytes. The cycle involves 1 feeder reaction to incorporate the ammonium and 4 reactions in the cycle. It prevents cytotoxicCytotoxicParvovirus B19hyperammonemiaHyperammonemiaElevated level of ammonia in the blood. It is a sign of defective catabolism of amino acids or ammonia to urea.Cirrhosis levels.
The catabolism of amino acidsAmino acidsOrganic 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) involves transaminationTransaminationTransamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2).Catabolism of Amino Acids and deaminationDeaminationThe removal of an amino group (NH2) from a chemical compound.Catabolism of Amino Acids reactions, which result in the release of ammoniaAmmoniaA 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 (NH3).
The regulation of nitrogen levels within the body is crucial due to the toxicityToxicityDosage Calculation of ammoniaAmmoniaA 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.
Excess nitrogen in the form of ammonium is then bonded to AAs via transaminationTransaminationTransamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2).Catabolism of Amino Acids reactions and transported to the liverLiverThe 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 kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy.
The most important AAs in nitrogen transport are glutamateGlutamateDerivatives 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 and alanineAlanineA 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.
Within the kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy, ammonium ions are released through glutamineGlutamineA 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 AcidsdeaminationDeaminationThe removal of an amino group (NH2) from a chemical compound.Catabolism of Amino Acids and excreted directly into the urine.
Within the liverLiverThe 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, the amino groups from alanineAlanineA 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 glutamateGlutamateDerivatives 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 are transferred via aminotransferases, resulting in ammoniaAmmoniaA 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 and aspartateAspartateOne 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, which are shunted into the urea cycle:
Involves1 feeder reaction (incorporation of ammonium and CO2) and 4 cycle reactions (creating 1 molecule of urea)
Overall reaction equation: NH3 + CO2 + aspartateAspartateOne 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 + 3 ATP + 2 H2O → urea + fumarateFumarateCitric Acid Cycle + 2 ADP + 2 Pi + AMP + PPi
Defects in any of the cycle’s catalyzing enzymesEnzymesEnzymes 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 result in hyperammonemiaHyperammonemiaElevated level of ammonia in the blood. It is a sign of defective catabolism of amino acids or ammonia to urea.Cirrhosis.
Nitrogen is produced in skeletal musculature via the catabolism of proteinsProteinsLinear 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. It is bound to AAs in the form of amino groups → bloodstream → liverLiverThe 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.
Nitrogen can be synthesized in the liverLiverThe 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 from intermediate byproducts of the citric acid cycleCitric acid cycleThe 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.
Nitrogen can also be produced in the intestines by bacteriaBacteriaBacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology or via the breakdown of dietary protein, then shunted directly to the liverLiverThe 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 via the venous portal system.
GlutamateGlutamateDerivatives 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 (or glutamic acid) is essential for nitrogen transport to the kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy and liverLiverThe 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.
Forms in peripheral cells by transaminationTransaminationTransamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2).Catabolism of Amino Acids to an α-ketoglutarate
Can receive another amino group via glutamine synthetaseGlutamine synthetaseSynthesis of Nonessential Amino Acids → glutamineGlutamineA 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:
In the kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy, glutaminase deaminates glutamineGlutamineA 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, releasing ammonium ions into the urine.
In the liverLiverThe 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, glutamineGlutamineA 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 releases ammonium ions via glutamateGlutamateDerivatives 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 dehydrogenase, which are shunted into the urea cycle.
Can also be converted into alanineAlanineA 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 via transaminationTransaminationTransamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2).Catabolism of Amino Acids
AlanineAlanineA 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 is essential for nitrogen transport from the muscles to the liverLiverThe 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.
Forms when glutamateGlutamateDerivatives 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 transfers its amino group to pyruvatePyruvateDerivatives of pyruvic acid, including its salts and esters.Glycolysis → alanineAlanineA 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
This reaction reverts within the liverLiverThe 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:
Resulting pyruvatePyruvateDerivatives of pyruvic acid, including its salts and esters.Glycolysis is used in gluconeogenesisGluconeogenesisGluconeogenesis 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 → glucoseGlucoseA 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, which is released into the bloodstream and used again in skeletal muscle (glucose-alanine or Cahill cycle).
Resulting glutamateGlutamateDerivatives 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 can be used to release ammoniaAmmoniaA 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 via deaminationDeaminationThe removal of an amino group (NH2) from a chemical compound.Catabolism of Amino Acids OR convert oxaloacetateOxaloacetateDerivatives 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 into aspartateAspartateOne 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 via transaminationTransaminationTransamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2).Catabolism of Amino Acids; both products are shunted into the urea cycle.
Urea cycle takes place exclusively in the liverLiverThe 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, within the mitochondriaMitochondriaSemiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes.The Cell: Organelles and cytosolCytosolA cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement.The Cell: Cytosol and Cytoskeleton of hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy.
Nitrogen atoms reach the liverLiverThe 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 in the form of amino groups bound to AAs (alanineAlanineA 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 or glutamateGlutamateDerivatives 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).
Involves 1 feeder reaction and 4 cycle reactions, and requires 3 ATP
Reaction steps of the urea cycle
Step 1 or feeder reaction: ammoniaAmmoniaA 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 (NH3) + CO2 → carbamoyl phosphatePhosphateInorganic salts of phosphoric acid.Electrolytes
In the mitochondria, catalyzed by carbamoyl phosphate synthetase, requires N-acetylglutamate as an activator and 2 ATP
In the mitochondriaMitochondriaSemiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes.The Cell: Organelles, catalyzed by ornithine carbamoyltransferase
Step 3: citrulline + aspartateAspartateOne 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 → argininosuccinate
In the cytosolCytosolA cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement.The Cell: Cytosol and Cytoskeleton, catalyzed by argininosuccinate synthetase, requires 1 ATP
In the cytosolCytosolA cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement.The Cell: Cytosol and Cytoskeleton, catalyzed by argininosuccinate lyase
FumarateFumarateCitric Acid Cycle either enters the CAC or transforms into oxaloacetateOxaloacetateDerivatives 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, which can be turned into aspartateAspartateOne 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 and re-enter the urea cycle (aspartateAspartateOne 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 cycle).
Step 5: arginine + H2O → urea + ornithine
In cytosolCytosolA cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement.The Cell: Cytosol and Cytoskeleton, catalyzed by arginase
Urea enters the bloodstream.
Ornithine is transported back into the mitochondrial matrix → step 2.
Net reaction per cycle: 2 NH3 + CO2 + 3 ATP + H2O → urea + 2 ADP + 4 Pi + AMP
Approximately 30 g of urea are produced → bloodstream every day (varies greatly according to diet)
Urea is soluble in water → the kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy → excreted in the urine (biggest portion of the nitrogen-containing compounds is in the urine)
Ornithine transcarbamylase (OTC) deficiency: X-linked recessiveX-Linked RecessiveDuchenne Muscular Dystrophy condition considered to be the most common type of urea cycle disorder in humans. PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship suffering from this congenital disorder lose the ability to eliminate ammoniaAmmoniaA 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 due to a lack of OTC. The high levels of ammoniaAmmoniaA 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 caused by this condition produce a comaComaComa is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma in newborns within 72 hours of birth.
Acquired conditions that affect the urea cycle
Acute and chronic liverLiverThe 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 diseases: caused by hepatic parenchymal necrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage leading to hepatic encephalopathyEncephalopathyHyper-IgM Syndrome, attributed to hyperammonemiaHyperammonemiaElevated level of ammonia in the blood. It is a sign of defective catabolism of amino acids or ammonia to urea.Cirrhosis because of the liverLiverThe 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’s inability to metabolize ammoniaAmmoniaA 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 by the urea cycle. The liverLiverThe 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’s synthetic functions are defective, so there is often a concomitant coagulopathy. JaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice occurs because of the impaired conjugationConjugationA parasexual process in bacteria; algae; fungi; and ciliate eukaryota for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a unidirectional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes.Bacteriology of bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism and excretion of the conjugated product.
Acute liver failureLiver failureSevere inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio.Autoimmune Hepatitis: usually caused by hepatotoxins or viral infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease. In the USA and UK, acetaminophen overdoseAcetaminophen OverdoseAcetaminophen (APAP) is an over-the-counter nonopioid analgesic and antipyretic medication. Acetaminophen is the most commonly used analgesic worldwide. Acetaminophen overdose is also one of the most common causes of medication poisoning and death. Acetaminophen Overdose is the most common cause, while viral hepatitis predominates in AsiaASIASpinal Cord Injuries.
Advanced liver failureLiver failureSevere inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio.Autoimmune Hepatitis in cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis: a condition caused by chronic damage and fibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans, with liverLiverThe 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 insufficiency evident in the advanced stages. Common causes of cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis include chronic viral hepatitis (hepatitis BHepatitis BHepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus, C), alcoholicAlcoholicPersons who have a history of physical or psychological dependence on ethanol.Mallory-Weiss Syndrome (Mallory-Weiss Tear)liverLiverThe 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, hemochromatosisHemochromatosisA disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption.Hereditary Hemochromatosis, and nonalcoholic fatty liverNonalcoholic fatty liverFatty liver finding without excessive alcohol consumption.Nonalcoholic Fatty Liver Disease disease.
References
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Häberle, J., Boddaert, N., Burlina, A., Chakrapani, A., Dixon, M., Huemer, M., Karall, D., Martinelli, D., Crespo, P. S., Santer, R., Servais, A., Valayannopoulos, V., Lindner, M., Rubio, V., & Dionisi-Vici, C. (2012). Suggested guidelines for the diagnosis and management of urea cycle disordersUrea cycle disordersUrea cycle disorders (UCDs) are caused by genetic defects and result in deficiencies of enzymes and transporters of the urea cycle. As a result of the defects, individuals are unable to rid the body of nitrogen waste. Common symptoms include vomiting, lethargy, seizures, and respiratory alkalosis.Urea Cycle Disorders. Orphanet Journal of Rare Diseases, 7(1), 32. https://doi.org/10.1186/1750-1172-7-32
Lehninger, A. L., Nelson, D. L., & Cox, M. M. (2021). Lehninger principles of biochemistry (8th ed.). W.H. Freeman and Company.
Mew, N. A., Simpson, K. L., Gropman, A. L., Lanpher, B. C., Chapman, K. A., & Summar, M. L. (2017). Urea cycle disordersUrea cycle disordersUrea cycle disorders (UCDs) are caused by genetic defects and result in deficiencies of enzymes and transporters of the urea cycle. As a result of the defects, individuals are unable to rid the body of nitrogen waste. Common symptoms include vomiting, lethargy, seizures, and respiratory alkalosis.Urea Cycle Disorders overview. In M. P. Adam, H. H. Ardinger, R. A. Pagon, S. E. Wallace, L. J. Bean, G. Mirzaa, & A. Amemiya (Eds.), GeneReviews®. University of Washington, Seattle.
Morris, S. M. (2002). Regulation of enzymesEnzymesEnzymes 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 of the urea cycle and arginine metabolism. Annual Review of Nutrition, 22(1), 87-105. https://doi.org/10.1146/annurev.nutr.22.110801.140547
Nagamani, S. C., Erez, A., & Lee, B. (2012). Argininosuccinate lyase deficiencyArgininosuccinate lyase deficiencyRare autosomal recessive disorder of the urea cycle which leads to the accumulation of argininosuccinic acid in body fluids and severe hyperammonemia. Clinical features of the neonatal onset of the disorder include poor feeding, vomiting, lethargy, seizures, tachypnea, coma, and death. Later onset results in milder set of clinical features including vomiting, failure to thrive, irritability, behavioral problems, or psychomotor retardation. Mutations in the argininosuccinate lyase gene cause the disorder.Urea Cycle Disorders. GeneticsGeneticsGenetics is the study of genes and their functions and behaviors.Basic Terms of Genetics in Medicine, 14(5), 501-507. https://doi.org/10.1038/gim.2011.1
Nussbaum, R. L., McInnes, R. R., & Willard, H. F. (2016). Thompson & Thompson geneticsGeneticsGenetics is the study of genes and their functions and behaviors.Basic Terms of Genetics in medicine (8th ed.). Elsevier.
Schimke, R. T. (1962). Adaptive characteristics of urea cycle enzymesEnzymesEnzymes 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 in the rat. Journal of Biological Chemistry, 237(2), 459-468.
Summar, M. L., & Tuchman, M. (2001). Proceedings of a consensus conference for the management of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with urea cycle disordersUrea cycle disordersUrea cycle disorders (UCDs) are caused by genetic defects and result in deficiencies of enzymes and transporters of the urea cycle. As a result of the defects, individuals are unable to rid the body of nitrogen waste. Common symptoms include vomiting, lethargy, seizures, and respiratory alkalosis.Urea Cycle Disorders. The Journal of Pediatrics, 138(1), S6-S10. https://doi.org/10.1067/mpd.2001.111836
Walker, V. (2009). AmmoniaAmmoniaA 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 BalancetoxicityToxicityDosage Calculation and its prevention in inherited defects of the urea cycle. DiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus, ObesityObesityObesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity and Metabolism, 11(9), 823-835. https://doi.org/10.1111/j.1463-1326.2009.01054.x
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