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Aliases | SAT1 , DC21, KFSD, KFSDX, SAT, SSAT, SSAT-1, spermidine/spermine N1-acetyltransferase 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 313020 MGI: 98233 HomoloGene: 37716 GeneCards: SAT1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Diamine acetyltransferase 1 is an enzyme that in humans is encoded by the SAT1 gene found on the X chromosome. [4] [5] [6]
Spermidine/spermine N(1)-acetyltransferase (SPD/SPM acetyltransferase) is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the N(1)-acetylation of spermidine and spermine and, by the successive activity of polyamine oxidase, spermine can be converted to spermidine and spermidine to putrescine. [6] The SAT1 gene is used to help regulate polyamine levels inside the cell by regulating their transport in and out of the cell. [7] [8] SAT1 is also involved in the first step to synthesize N-acetylputrescine from putrescine. [9] PMF1 and NRF2 work together to transcript the SAT1 gene. [10]
The SAT1 gene is 3,069 base pairs long. There are 171 amino acids and its molecular mass is 20024 Da (daltons). In 1992 at The Johns Hopkins University School of Medicine, Lei Xiao and several others cloned over 4000 base pairs of the region containing the coding sequence of the SAT1 gene also referred to as SSAT-1, SSAT, SAT, KFSD, DC21, KFSDX gene. [11] This gene is located on the X chromosome in the region Xp22.1. The primer extension analysis indicated that the transcription started 179 bases upstream from the translational start site. Furthermore, they determined that it appeared to be controlled by a "TATA-less" promoter. Normally, there would be a TATA box where RNA polymerase II would be involved in assisting with initiation by properly positioning the enzyme, however in a TATA-less promoter situation the TATA box is absent. [12]
An association with keratosis follicularis spinulosa decalvans (KFSD) has been suggested. [13] Data shows that keratosis follicularis spinulosa decalvans could be caused by mutations in the SAT 1 gene. KSFD is also believed to be X-linked, which helps prove that the disease is caused by a mutation found in the SAT 1 gene which is located on the X chromosome. [14] The mutation most likely occurs at the location Xp22.1. [15] KDSF mostly affects men, which makes sense for it to be an X-linked disease, caused by a mutation of the SAT1 gene. [16]
Elevated levels of RNA transcripts of SAT1 in the bloodstream have been associated with a higher risk of suicide. [17] [18] [19]
The SAT1 gene has implications with NLS-2 Neu–Laxova syndrome, type 2 (NLS). It is inherited as an autosomal recessive trait and is considered a rare lethal congenital disorder. Severe growth delays before birth including low birth weight and shorter than normal length occur. After birth, outward observable characteristics include significant small skull size (microcephaly), wider than normal spaced eyes, sloped forehead and other disfiguring facial features. There may also be random places of fluid retention (edema) throughout the body and permanent joint limitations due to limb malformations. NLS can be detected in pregnant woman with ultrasound examination. In some people of Neu-Laxova syndrome, other areas were severely affected such as skin, genitals, and other internal organs including the heart. Males and females are equally affected and could be most closely associated with persons of Pakistani origin. However, there have been cases reported in several other diverse backgrounds. The prognosis is extremely poor and in most cases the infant dies shortly after birth or are stillborn. The first documented and reported case in Japan involved a baby girl exhibiting microcephaly, severe edema, and other symptoms. In her case she had a condition known as congenital vertical talus or rocker-feet. The foot is abnormally shaped in a convex position. She survived 134 days. [20] [21] [22]
The SAT1 gene plays a vital role in the catabolic pathway of polyamine metabolism. It acts as a rate-limiting enzyme in the pathway of polyamine metabolism, meaning it is significant in the involvement of cell survival. Research has shown that the tumor protein known as p53 can specifically target the SAT1 gene that results in ferroptotic cell-death. Ferroptosis is when a death of a cell is caused by an iron-dependent accumulation of a lipid. [23]
Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of putrefying flesh, but also contributes to other unpleasant odors.
The enzyme ornithine decarboxylase catalyzes the decarboxylation of ornithine to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids and forms a homodimer.
Spermine is a polyamine involved in cellular metabolism that is found in all eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some bacteria as well. It is found as a polycation at physiological pH. Spermine is associated with nucleic acids and is thought to stabilize helical structure, particularly in viruses. It functions as an intracellular free radical scavenger to protect DNA from free radical attack. Spermine is the chemical primarily responsible for the characteristic odor of semen.
Spermidine is a polyamine compound found in ribosomes and living tissues and having various metabolic functions within organisms. It was originally isolated from semen.
Spermidine synthase is an enzyme that catalyzes the transfer of the propylamine group from S-adenosylmethioninamine to putrescine in the biosynthesis of spermidine. The systematic name is S-adenosyl 3-(methylthio)propylamine:putrescine 3-aminopropyltransferase and it belongs to the group of aminopropyl transferases. It does not need any cofactors. Most spermidine synthases exist in solution as dimers.
SAT1 may refer to:
The enzyme adenosylmethionine decarboxylase catalyzes the conversion of S-adenosyl methionine to S-adenosylmethioninamine. Polyamines such as spermidine and spermine are essential for cellular growth under most conditions, being implicated in many cellular processes including DNA, RNA and protein synthesis. S-adenosylmethionine decarboxylase (AdoMetDC) plays an essential regulatory role in the polyamine biosynthetic pathway by generating the n-propylamine residue required for the synthesis of spermidine and spermine from putrescein. Unlike many amino acid decarboxylases AdoMetDC uses a covalently bound pyruvate residue as a cofactor rather than the more common pyridoxal 5'-phosphate. These proteins can be divided into two main groups which show little sequence similarity either to each other, or to other pyruvoyl-dependent amino acid decarboxylases: class I enzymes found in bacteria and archaea, and class II enzymes found in eukaryotes. In both groups the active enzyme is generated by the post-translational autocatalytic cleavage of a precursor protein. This cleavage generates the pyruvate precursor from an internal serine residue and results in the formation of two non-identical subunits termed alpha and beta which form the active enzyme.
Spermine synthase is an enzyme that converts spermidine into spermine. This enzyme catalyses the following chemical reaction
A polyamine oxidase (PAO) is an enzymatic flavoprotein that oxidizes a carbon-nitrogen bond in a secondary amino group of a polyamine donor, using molecular oxygen as an acceptor. The generalized PAO reaction converts three substrates into three products. Different PAOs with varying substrate specificities exist in different organisms. Phylogenetic analyses suggest that PAOs likely evolved once in eukaryotes and diversified by divergent evolution and gene duplication events, though some prokaryotes have acquired PAOs through horizontal gene transfer.
In enzymology, a diamine N-acetyltransferase is an enzyme that catalyzes the chemical reaction
Polyamine-modulated factor 1 is a protein that in humans is encoded by the PMF1 gene.
Spermine oxidase is an enzyme that in humans is encoded by the SMOX gene.
Peroxisomal N(1)-acetyl-spermine/spermidine oxidase is an enzyme that in humans is encoded by the PAOX gene.
Diamine acetyltransferase 2 is an enzyme that in humans is encoded by the SAT2 gene. SAT2 maintains a key metabolic glutamine/glutamate balance underpinning retrograde signaling by dendritic release of the neurotransmitter glutamate.
Keratosis follicularis spinulosa decalvans is a rare X-linked disorder described by Siemens in 1926. It is a disease that begins in infancy with keratosis pilaris localized on the face, then evolves to more diffuse involvement.
A polyamine is an organic compound having more than two amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. Most aromatic polyamines are crystalline solids at room temperature.
N1-acetylpolyamine oxidase (EC 1.5.3.13, hPAO-1, mPAO, hPAO) is an enzyme with systematic name N1-acetylpolyamine:oxygen oxidoreductase (3-acetamidopropanal-forming). This enzyme catalyses the following chemical reaction
Spermine oxidase (EC 1.5.3.16, PAOh1/SMO, AtPAO1, AtPAO4, SMO) is an enzyme with systematic name spermidine:oxygen oxidoreductase (spermidine-forming). This enzyme catalyses the following chemical reaction
Non-specific polyamine oxidase (EC 1.5.3.17, polyamine oxidase, Fms1, AtPAO3) is an enzyme with systematic name polyamine:oxygen oxidoreductase (3-aminopropanal or 3-acetamidopropanal-forming). This enzyme catalyses the following chemical reaction
BpsA is a single-module non-ribosomal peptide synthase (NRPS) located in the cytoplasm responsible for the process of creating branched-chain polyamines, and producing spermidine and spermine. It has a singular ligand in its structure involved with Fe3+ and PLIP interactions. As seen by its EC number, it is a transferase (2) that transfers an alkyl or aryl group other than methyl groups (5) (2.5.1). BpsA was first discovered in the archaea Methanococcus jannaschii and thermophile Thermococcus kodakarensis and since then has been used in a variety of applications such as being used as a reporter, researching phosphopantetheinyl transferase (PPTase), and for NRPS domain recombination experiments it can be used as a model. Both (hyper)thermophilic bacteria and euryarchaeotal archaea seem to conserve BpsA and orthologs as branches chains polyamines are crucial for survival. There is also a second type of BpsA also known as Blue-pigment indigoidine synthetase that produces the pigment indigoidine and is found in organisms like Erwinia chrysanthemi. However, not much seems to be known about this variant except that it is a synthase, and it does not yet appear to be classified under an EC number.