Sorbitol dehydrogenase (or SDH) is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

. In humans this protein is encoded by the SORD gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Sorbitol dehydrogenase is an enzyme in carbohydrate metabolism

Carbohydrate metabolism

Carbohydrate metabolism denotes the various biochemical processes responsible for the formation, breakdown and interconversion of carbohydrates in living organisms....

 converting sorbitol

Sorbitol

Sorbitol, also known as glucitol, Sorbogem® and Sorbo®, is a sugar alcohol that the human body metabolizes slowly. It can be obtained by reduction of glucose, changing the aldehyde group to a hydroxyl group. Sorbitol is found in apples, pears, peaches, and prunes...

, the sugar alcohol

Sugar alcohol

A sugar alcohol is a hydrogenated form of carbohydrate, whose carbonyl group has been reduced to a primary or secondary hydroxyl group . Sugar alcohols have the general formula Hn+1H, whereas sugars have HnHCO...

 form of glucose

Glucose

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

, into fructose

Fructose

Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

. Together with aldose reductase

Aldose reductase

Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the reduction of a variety of aldehydes and carbonyls, including monosaccharides...

, it provides a way for the body to produce fructose from glucose without using ATP

Adenosine triphosphate

Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

. Sorbitol dehydrogenase uses NAD

NAD

NAD may refer to:* No abnormality detected, a medical status description* No apparent distress, a status description in childbirth* NAD Electronics, a Canadian audio equipment manufacturer...

⁺ as a cofactor; its reaction is sorbitol + NAD⁺ --> fructose + NADH + H⁺. 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 is also involved in catalysis. Organs that use it most frequently include the 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...

 and seminal vesicle

Seminal vesicle

The seminal vesicles or vesicular glands are a pair of simple tubular glands posteroinferior to the urinary bladder of male mammals...

; it is found in all kinds of organisms from 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...

 to humans. A secondary use is the metabolism

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 of dietary sorbitol

Sorbitol

Sorbitol, also known as glucitol, Sorbogem® and Sorbo®, is a sugar alcohol that the human body metabolizes slowly. It can be obtained by reduction of glucose, changing the aldehyde group to a hydroxyl group. Sorbitol is found in apples, pears, peaches, and prunes...

, though sorbitol

Sorbitol

Sorbitol, also known as glucitol, Sorbogem® and Sorbo®, is a sugar alcohol that the human body metabolizes slowly. It can be obtained by reduction of glucose, changing the aldehyde group to a hydroxyl group. Sorbitol is found in apples, pears, peaches, and prunes...

 is known not to absorb as well in the intestine as its related compounds glucose and fructose, and is usually found in quite small amounts in the diet anyway (except when used as an artificial sweetener).

Structure

The structure of human sorbitol dehydrogenase was determined through crystallization experiments and X-ray diffraction (with a resolution of 2.20 Å). The method used for crystallization was “Vapor Diffusion, Hanging Drop” at pH 6.2 and at a temperature of 295.0 K. Sorbitol dehydrogenase consists of four identical chains (A, B, C, D), each of which is 31% helical (14 helices) and 26% beta sheet (23 strands). MolProbity Ramachandran analysis was conducted by Lovell, Davis, et al. The results were that 97.1% of all residues were in favored regions and 100.0% of all residues were in allowed regions, with no outliers. All four chains have 356 residues each and a catalytic site. The catalytic sites contain both a serine and a histidine residue, which are hydrophilic sidechains. The residues require NAD+ and a zinc ion to be present for catalytic activity. Sorbitol dehydrogenase belongs to the oxidoreductase family, which means it helps catalyze oxidation reduction reactions. As stated above, the enzyme helps in the pathway of converting glucose into fructose.

Subunit interactions in SDH

The interactions between subunits forming a tetramer in SDH is determined by non covalent interaction. These non covalent interactions consists of an hydrophobic effect, hydrogen bonds and electrostatic interactions between the four identical subunits. For homotetrameric proteins such as SDH, the structure is believed to have evolved going from a monomeric to a dimeric and finally toward a tetrameric structure in evolution. The SDH proteins are evolutionary closely related to alcohol dehydrogenase

Alcohol dehydrogenase

Alcohol dehydrogenases are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide...

which also belongs to the protein superfamily of medium chain dehydrogenase/reductase enzymes (MDRs). Mammalian ADHs are all dimeric enzymes but certain bacterial ADHs also share a tetrameric quaternary structure. SDH from silver leaf whitefly and yeast ADH1 both lacks a structural zinc site and shares a tetrameric quaternary structure, thus showing a close evolutionary relationship from a structural viewpoint between the two classes of proteins (ADH and SDH).

The general binding process in SDH is described by the gain in free energy which can be determined from the rate of association and dissociation between subunits.

The following image shows the assembly of the four subunits (A,B,C and D) in SDH.
A hydrogen bonding network between subunits has been shown to be important for the stability of the tetrameric quaternary protein structure. For example a study of SDH which used diverse methods such as protein sequence alignments, structural comparisons, energy calculations, gelfiltration experiments and enzyme kinetics experiments, could reveal an important hydrogen bonding network which stabilizes the tetrameric quaternary structure in mammalian SDH.