Branched-chain alpha-keto acid dehydrogenase complex
Encyclopedia
The branched-chain α-keto acid dehydrogenase complex is a combination of enzyme
s responsible for the degradation of the branched-chain amino acids
. Examples of these include valine
, isoleucine
, and leucine
.
and the pyruvate dehydrogenase complex creating acetyl-CoA
prior to the citric acid cycle.
of the complex as a whole is responsible for maple syrup urine disease
.
This enzyme is an autoantigen recognized in primary biliary cirrhosis
, a form of acute liver failure. These antibodies appear to recognize oxidized protein
that has resulted from inflammatory immune responses. Some of these inflammatory responses are explained by gluten sensitivity
.. Other mitochondrial autoantigens
include pyruvate dehydrogenase
and branched chain oxoglutarate dehydrogenase
, which are antigens recognized by anti-mitochondrial antibodies
.
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 responsible for the degradation of the branched-chain amino acids
Branched-chain amino acids
A branched-chain amino acid is an amino acid having aliphatic side-chains with a branch...
. Examples of these include valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
, isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
, and leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
.
Cofactors
This complex requires the following 5 cofactors:- Thiamine diphosphate
- FADFADIn biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate...
- NAD+Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...
- LipoateLipoic acidLipoic acid , also known as α-lipoic acid and Alpha Lipoic Acid is an organosulfur compound derived from octanoic acid. LA contains two vicinal sulfur atoms attached via a disulfide bond and is thus considered to be oxidized...
- Coenzyme ACoenzyme ACoenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
Similar enzymes
This complex is also analogous to the alpha-ketoglutarate dehydrogenase complex in the citric acid cycleCitric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
and the pyruvate dehydrogenase complex creating acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
prior to the citric acid cycle.
Pathology
A deficiency in any of the enzymes of this complex as well as an inhibitionEnzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of the complex as a whole is responsible for maple syrup urine disease
Maple syrup urine disease
Maple syrup urine disease , also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia...
.
This enzyme is an autoantigen recognized in primary biliary cirrhosis
Primary biliary cirrhosis
Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...
, a form of acute liver failure. These antibodies appear to recognize oxidized 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...
that has resulted from inflammatory immune responses. Some of these inflammatory responses are explained by gluten sensitivity
Gluten sensitivity
Gluten sensitivity belongs to a spectrum of disorders in which gluten has an adverse effect on the body. It can be defined as a non-allergic and non-autoimmune condition in which the consumption of gluten can lead to symptoms similar to those observed in coeliac disease or wheat allergy .Gluten...
.. Other mitochondrial autoantigens
include pyruvate dehydrogenase
Pyruvate dehydrogenase
Pyruvate dehydrogenase complex is a complex of three enzymes that transform pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the...
and branched chain oxoglutarate dehydrogenase
Oxoglutarate dehydrogenase
The oxoglutarate dehydrogenase complex or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle.-Units:...
, which are antigens recognized by anti-mitochondrial antibodies
Anti-mitochondrial antibodies
Anti-mitochondrial antibodies are autoantibodies, consisting of immunoglobulins formed against mitochondria, primarily mitochondria in cells of the liver...
.