enzymology Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

, a butyrate kinase () is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that

catalyzes Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

the

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

:ADP + butyryl-phosphate

\rightleftharpoons

ATP + butyrate Thus, the two substrates of this enzyme are ADP and butyryl-phosphate, whereas its two

products Product may refer to: Business * Product (business), an item that serves as a solution to a specific consumer problem. * Product (project management), a deliverable or set of deliverables that contribute to a business solution Mathematics * Produ ...

are ATP and

butyrate The conjugate acids are in :Carboxylic acids. {{Commons category, Carboxylate ions, Carboxylate anions Carbon compounds Oxyanions ...

. This enzyme belongs to the family of

transferase A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of di ...

s, specifically those transferring phosphorus-containing groups (

phosphotransferase Phosphotransferases are a category of enzymes ( EC number 2.7) that catalyze phosphorylation reactions. The general form of the reactions they catalyze is: :A-P + B \rightleftharpoons B-P + A Where ''P'' is a phosphate group and A and B are the do ...

s) with a carboxy group as acceptor. The

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial ...

of this enzyme class is ATP:butanoate 1-phosphotransferase. This enzyme participates in butyrate metabolism. This enzyme is transcribed from the gene '' buk'', which is part of the ASKHA super family.

Mechanism

:ADP + butyryl-phosphate

\rightleftharpoons

ATP + butyrate The reaction above is a

nucleophilic substitution In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...

reaction. An electron pair from an oxygen on ADP attacks the phosphorus on butyryl-phosphate, breaking the bond between phosphorus and oxygen to create ATP and butyrate. The arrow-pushing mechanism is shown above. The reaction can also occur in the reverse direction, as shown below, under certain fermentation conditions. :ATP + butyrate

\rightleftharpoons

ADP + butyryl-phosphate

Structure

As of 2015, two

structures A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

have been solved for this class of enzymes, with PDB accession codes and . The study conducted to solve 1SAZ was retracted in 2012 due to fact that the data was used without the permission of the sole custodian. The investigators of the study that produced the crystallization of 1X9J hypothesized that the enzyme was an octomer formed from dimers. The crystallized form has a radius of 7.5 nm which corresponded to a

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

of 380

kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at ...

. Because a

monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...

of ''buk2'' is about 43 kDa, it was believed that the enzyme itself was either an octomer or a

nonamer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relative ...

. Investigators hypothesized that the enzyme was an octomer since most of the proteins within the ASHKA super family form dimers.

Function

Butyrate kinase is active within the human colon. To form butyrate, two molecules of

acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...

are combined and reduced to produce

butyryl-CoA Butyryl-coenzyme A (or butyryl-CoA) is the coenzyme A-containing derivative of butyric acid. It is acted upon by butyryl-CoA dehydrogenase and an intermediary compound of ABE fermentation. Butyryl-CoA is a precursor to and converted from crotonyl- ...

. Butyryl CoA is then converted into butyrate through two reactions. The first reaction converts butyryl-CoA to butyryl-phosphate by using the phosphotransbutyrylase enzyme. Butyryl-phosphate is then converted into butyrate by using butyrate kinase and in the process, releases ATP. Butyrate plays an important role within cells as it affects

cellular proliferation Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...

, differentiation, and

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

. Because of the significant roles that butyrate plays within cells, it is essential that butyrate kinase is functioning correctly, which can be done through regulation of the enzyme. One study has previously found that butyrate kinase is not regulated by its end-products or other acids such as acetic acid, but more studies need to be conducted to further elucidate the regulation of butyrate kinase.

Disease relevance

As stated in the previous section, butyrate is involved with multiple cellular functions. Because of its involvement with these functions, it is hypothesized that butyrate can act as a protective agent against

colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...

and various

inflammatory bowel diseases Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well a ...

. Butyrate plays a key role in colon cancer by switching its role concerning cellular proliferation and apoptosis depending on the state and conditions of the cell. Butyrate also possesses anti-inflammatory effects to decrease colonic inflammation such as

ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...

. One study specifically identified the

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

NF-kB as a target of butyrate to decrease the number of pro-inflammatory cytokines.

Mechanism

Structure

Function

Disease relevance

References

Further reading