Module 16: Amino Acid Oxidation and the Production of Urea

Alanine aminotransferase

An enzyme that catalyzes the reversible transamination between alanine and pyruvate, using glutamate and α-ketoglutarate as the other amino acid/α-keto acid pair.

Aldimine

A compound containing a carbon-nitrogen double bond with the nitrogen atom connected to an alkyl or aryl group, also known as a Schiff base.

Aminotransferase

An enzyme that catalyzes the transfer of an amino group from one molecule to another, also known as a transaminase.

Ammonotelic

Organisms that excrete nitrogenous waste primarily as ammonia.

Arginase

An enzyme that catalyzes the hydrolysis of arginine to ornithine and urea, the final step in the urea cycle.

Argininosuccinate

An intermediate in the urea cycle, formed from the condensation of citrulline and aspartate.

Argininosuccinate synthetase

An enzyme that catalyzes the formation of argininosuccinate from citrulline and aspartate, requiring ATP.

Aspartate-argininosuccinate shunt

A series of reactions that connect the urea cycle to the citric acid cycle.

Biotin

A coenzyme involved in carboxylation reactions, particularly in the transfer of carbon dioxide.

Branched-chain α-keto acid dehydrogenase complex

An enzyme complex that catalyzes the oxidative decarboxylation of branched-chain α-keto acids derived from leucine, isoleucine, and valine.

Carbamoyl phosphate

A high-energy compound that donates a carbamoyl group in metabolic reactions, including the urea cycle.

Carbamoyl phosphate synthetase I

An enzyme that catalyzes the formation of carbamoyl phosphate from ammonia and bicarbonate, requiring two ATP molecules.

Cholecystokinin (CCK)

A hormone secreted by the duodenum that stimulates the release of digestive enzymes from the pancreas and bile from the gallbladder.

Citrulline

An amino acid that is an intermediate in the urea cycle.

Enteropeptidase

An enzyme found in the small intestine that activates trypsinogen to trypsin, initiating the activation cascade of pancreatic proteases.

Essential amino acids

Amino acids that cannot be synthesized by the body and must be obtained from the diet.

Folate

The oxidized form of tetrahydrofolate, a coenzyme involved in one-carbon transfer reactions.

Gastrin

A hormone secreted by the stomach that stimulates the production of gastric acid and pepsinogen.

Glucogenic amino acids

Amino acids that can be converted into glucose through gluconeogenesis.

Glucose-alanine cycle

A cycle in which alanine transfers nitrogen from muscle to the liver, where it is converted to urea, and pyruvate from alanine is used to synthesize glucose, which is returned to the muscle.

Glutamate

An amino acid that plays a central role in nitrogen metabolism, acting as a collector of amino groups from other amino acids.

Glutamate dehydrogenase

An enzyme that catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate and ammonia.

Glutaminase

An enzyme that catalyzes the hydrolysis of glutamine to glutamate and ammonia.

Glutamine

An amino acid that serves as a non-toxic carrier of ammonia in the bloodstream.

Glutamine synthetase

An enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia, requiring ATP.

Glycine cleavage enzyme

An enzyme complex that catalyzes the oxidative cleavage of glycine to carbon dioxide, ammonia, and a methylene group, requiring tetrahydrofolate.

Homogentisate dioxygenase

An enzyme involved in the degradation of tyrosine and phenylalanine; a deficiency in this enzyme leads to alkaptonuria.

Ketogenic amino acids

Amino acids that can be degraded into acetyl-CoA or acetoacetyl-CoA, which can be used for ketone body synthesis.

Maple syrup urine disease

A genetic disorder caused by a deficiency in the branched-chain α-keto acid dehydrogenase complex, leading to the accumulation of branched-chain amino acids and their α-keto acids in the urine.

Megaloblastic anemia

A type of anemia characterized by the presence of large, immature red blood cells (megaloblasts) in the bone marrow, often caused by deficiencies in vitamin B12 or folate.

Methionine adenosyl transferase

An enzyme that catalyzes the synthesis of S-adenosylmethionine (adoMet) from methionine and ATP.

N-Acetylglutamate

An allosteric activator of carbamoyl phosphate synthetase I, regulating the urea cycle.

Ornithine

An amino acid that participates in the urea cycle, accepting a carbamoyl group from carbamoyl phosphate.

Ornithine transcarbamoylase

An enzyme that catalyzes the transfer of a carbamoyl group from carbamoyl phosphate to ornithine, forming citrulline.

Pancreatic trypsin inhibitor

A protein that inhibits the activity of trypsin, preventing premature activation of pancreatic proteases.

Pepsin

A digestive enzyme secreted by the stomach that breaks down proteins into smaller peptides.

Pepsinogen

The inactive precursor of pepsin, activated by the acidic environment of the stomach.

Pernicious anemia

A type of anemia caused by a deficiency in vitamin B12, often due to a lack of intrinsic factor, which is necessary for vitamin B12 absorption.

Phenylalanine hydroxylase

An enzyme that catalyzes the conversion of phenylalanine to tyrosine, requiring tetrahydrobiopterin as a cofactor; a deficiency in this enzyme leads to phenylketonuria.

Phenylketonuria (PKU)

A genetic disorder caused by a deficiency in phenylalanine hydroxylase, leading to the accumulation of phenylalanine in the blood and neurological damage.

Pyridoxal phosphate (PLP)

The active form of vitamin B6, acting as a coenzyme for many enzymes involved in amino acid metabolism, including aminotransferases.

Pyridoxamine phosphate

The aminated form of pyridoxal phosphate, which can donate its amino group to an α-keto acid.

S-Adenosylhomocysteine

The product formed after S-adenosylmethionine donates its methyl group.

S-Adenosylmethionine (adoMet)

A coenzyme involved in methyl group transfer reactions.

Secretin

A hormone secreted by the duodenum that stimulates the pancreas to release bicarbonate, neutralizing the acidic chyme from the stomach.

Serine dehydratase

An enzyme that catalyzes the conversion of serine to pyruvate.

Tetrahydrobiopterin

A cofactor involved in the hydroxylation of phenylalanine to tyrosine by phenylalanine hydroxylase.

Tetrahydrofolate (H4 folate)

A coenzyme that carries one-carbon units in various oxidation states, participating in a variety of metabolic reactions.

Transamination

The transfer of an amino group from an amino acid to an α-keto acid, catalyzed by aminotransferases.

Transdeamination

A coupled reaction involving transamination and deamination, resulting in the removal of an amino group as ammonia.

Trypsin

A pancreatic protease that cleaves peptide bonds on the carboxyl side of lysine and arginine residues.

Trypsinogen

The inactive precursor of trypsin, activated by enteropeptidase in the small intestine.

Urea

The major nitrogenous waste product in mammals, formed in the liver through the urea cycle.

Urea cycle

A metabolic pathway in the liver that converts ammonia to urea, detoxifying ammonia.

Ureotelic

Organisms that excrete nitrogenous waste primarily as urea.

Uricotelic

Organisms that excrete nitrogenous waste primarily as uric acid.

Zymogen

An inactive precursor of an enzyme, often activated by proteolytic cleavage.

Amino acid catabolism

Involves the breakdown of the amino group and the carbon skeleton.

Key step in amino acid catabolism

The removal of the α-amino group using a pyridoxal phosphate cofactor.

Ammonotelic

Animals that excrete nitrogen as ammonia, e.g., most aquatic species.

Ureotelic animals

Animals that excrete nitrogen as urea, e.g., most terrestrial animals.

Uricotelic animals

Animals that excrete nitrogen as uric acid, e.g., birds and reptiles.

Gastrin

A hormone that stimulates the secretion of HCl and pepsinogen in the stomach when dietary protein enters.

Pepsinogen

A zymogen that is converted to its active form, pepsin, by autocatalytic cleavage at low pH.

Secretin

Released in response to low pH in the small intestine, it stimulates the pancreas to secrete bicarbonate.

Cholecystokinin (CCK)

Released upon the arrival of peptides in the duodenum, it triggers the secretion of pancreatic proteases.

Pancreatic proteases

Include trypsinogen, chymotrypsinogen, and procarboxypeptidases A and B.

Enteropeptidase

Converts trypsinogen into its active form, trypsin, which then activates other zymogens.

Pancreatic trypsin inhibitor

Protects the pancreas from self-digestion by inhibiting any prematurely activated trypsin.

Aminotransferases

Catalyze the transfer of α-amino groups from amino acids to α-ketoglutarate.

Common acceptor for amino groups

α-ketoglutarate.

Pyridoxal phosphate (PLP)

A coenzyme used by all aminotransferases, derived from vitamin B6.

Function of PLP

Acts as a carrier for amino groups at the enzyme's active site.

Ammonia transport in the bloodstream

Ammonia is transported as glutamine.

Glutamine synthetase

Combines ammonia with glutamate to yield glutamine, a non-toxic form.

Glutaminase

Hydrolyzes glutamine back to glutamate and ammonia in the liver.

Glucose-alanine cycle

A pathway where alanine carries ammonia and pyruvate from skeletal muscles to the liver.

Role of glucose-alanine cycle

In the liver, ammonia is excreted, and pyruvate is used for gluconeogenesis, producing glucose.