Fructose-bisphosphate aldolase
Encyclopedia
In molecular biology, fructose-bisphosphate aldolase , is a glycolytic
enzyme that catalyses
the reversible aldol
cleavage or condensation of fructose-1,6-bisphosphate into dihydroxyacetone-phosphate and glyceraldehyde 3-phosphate
. There are two classes of fructose-bisphosphate aldolases with different catalytic mechanisms: class I enzyme
s are found in animals, do not require a metal ion, and are characterised by the formation of a Schiff base
intermediate
between a highly conserved active site
lysine
and a substrate carbonyl
group, while the class II enzymes are produced in bacteria
and fungi, and require an active-site divalent
metal ion.
In vertebrates, three forms of this enzyme are found: aldolase A is expressed
in muscle
, aldolase B
in liver
, kidney
, stomach
and intestine
, and aldolase C in brain
, heart
and ovary
. The different isozymes have different catalytic
functions: aldolases A and C are mainly involved in glycolysis
, while aldolase B is involved in both glycolysis
and gluconeogenesis
. Defects in aldolase B result in hereditary fructose intolerance
.
Class II aldolases, mainly found in prokaryotes and fungi, are homodimeric enzymes, which require a divalent
metal ion, generally zinc
, for their activity. The class II aldolase family of proteins also includes subfamilies containing the Escherichia coli
galactitol operon
protein, gatY, which catalyses
the transformation of tagatose 1,6-bisphosphate into glycerone phosphate and D-glyceraldehyde 3-phosphate ; and E. coli N-acetyl galactosamine operon protein, agaY, which catalyses the same reaction. There are two histidine
residue
s in the first half of the sequence of these enzymes that have been shown to be involved in binding a zinc
ion
.
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
enzyme that catalyses
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the reversible aldol
Aldol
An aldol or aldol adduct is a beta-hydroxy ketone or aldehyde, and is the product of aldol addition ....
cleavage or condensation of fructose-1,6-bisphosphate into dihydroxyacetone-phosphate and glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...
. There are two classes of fructose-bisphosphate aldolases with different catalytic mechanisms: class I enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s are found in animals, do not require a metal ion, and are characterised by the formation of a Schiff base
Schiff base
A Schiff base, named after Hugo Schiff, is a compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group, not hydrogen....
intermediate
Reaction intermediate
A reaction intermediate or an intermediate is a molecular entity that is formed from the reactants and reacts further to give the directly observed products of a chemical reaction. Most chemical reactions are stepwise, that is they take more than one elementary step to complete...
between a highly conserved active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
and a substrate carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
group, while the class II enzymes are produced in bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and fungi, and require an active-site divalent
Divalent
In chemistry, a divalent ion or molecule has a valence of two and thus can form two bonds with other ions or molecules. An older term for divalent is bivalent....
metal ion.
In vertebrates, three forms of this enzyme are found: aldolase A is expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
in muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
, aldolase B
Aldolase B
Aldolase B also known as fructose-bisphosphate aldolase B or liver-type aldolase is one of three isoenzymes of the class I fructose 1,6-bisphosphate aldolase enzyme , and plays a key role in both glycolysis and gluconeogenesis...
in liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
and intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
, and aldolase C in brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
and ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
. The different isozymes have different catalytic
Biocatalysis
Biocatalysis is the use of natural catalysts, such as protein enzymes, to perform chemical transformations on organic compounds. Both enzymes that have been more or less isolated and enzymes still residing inside living cells are employed for this task....
functions: aldolases A and C are mainly involved in glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
, while aldolase B is involved in both glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
and gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
. Defects in aldolase B result in hereditary fructose intolerance
Fructose intolerance
Hereditary fructose intolerance or fructose poisoning is a hereditary condition caused by a deficiency of liver enzymes that metabolise fructose...
.
Class II aldolases, mainly found in prokaryotes and fungi, are homodimeric enzymes, which require a divalent
Divalent
In chemistry, a divalent ion or molecule has a valence of two and thus can form two bonds with other ions or molecules. An older term for divalent is bivalent....
metal ion, generally zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
, for their activity. The class II aldolase family of proteins also includes subfamilies containing the Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
galactitol operon
Operon
In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...
protein, gatY, which catalyses
Biocatalysis
Biocatalysis is the use of natural catalysts, such as protein enzymes, to perform chemical transformations on organic compounds. Both enzymes that have been more or less isolated and enzymes still residing inside living cells are employed for this task....
the transformation of tagatose 1,6-bisphosphate into glycerone phosphate and D-glyceraldehyde 3-phosphate ; and E. coli N-acetyl galactosamine operon protein, agaY, which catalyses the same reaction. There are two histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
residue
Residue
Residue may refer to:* Residue , material remaining after a distillation or an evaporation, or portion of a larger molecule** In particular, in biology, often refers specifically to an amino acid...
s in the first half of the sequence of these enzymes that have been shown to be involved in binding a zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
.