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KAT2A (GCN5L2 or GCN5) is a histone acetyltransferase (HAT), which functions mainly as a transcriptional activator. GCN5L2 may be one of the enzymes involved in acetylation in vivo. GCN5 is expressed primarily in the embryo and newborn and is crucial for normal embryonic development. Hence, KAT2A appears to be significant for differentiation of embryonic-derived preadipocytes. GCN5 also functions as a repressor of NF-kappa-B by promoting ubiquitination of the NF-kappa-B subunit RELA in a HAT-independent manner. Loss of GCN5L2 leads to a high occurrence of apoptosis in the KAT2A mutants, which begins before the onset of morphological abnormality.

AGXT is expressed only in the liver and its protein is localized mostly in the peroxisomes, where it is involved in glyoxylate detoxification. Mutations in the AGXT gene, some of which alter subcellular targetting, have been linked to type I primary hyperoxaluria.

SORD enzyme is part of of the zinc-containing alcohol dehydrogenase family that is broadly expressed in kidney and in the lens eye. SORD enzymatically catalyzes the zinc-dependent interconversion of polyols, such as sorbitol and xylitol, to their respective ketoses.

GALE is an enzyme that participates as the third enzyme in the Leloir pathway of galactose metabolism. GALE is a homodimeric epimerase localized in bacterial, plant, and mammalian cells. GALE inhances the reverse chemical reaction, the conversion of UDP-glucose to UDP-galactose. UDP-galactose builds galactose-containing proteins and fats, which have a crucial part in chemical signaling, building cellular structures, transporting molecules, and producing energy.

UBE2L6 belongs to the E2 ubiquitin-conjugating enzyme family. UBE2L6 enzyme is very similar in its primary structure to the enzyme encoded by UBE2L3 gene. UBE2L6 catalyzes the covalent attachment of ubiquitin to other proteins. UBE2L6 functions in the e6/e6-ap-induced ubiquitination of p53/tp53.

MAT2A is an important enzyme in cellular metabolism and catalyzes the formation of S-adenosylmethionine (SAMe) from L-methionine and ATP. MAT2A is expressed in extrahepatic tissues. In liver, MAT2A expression associates with growth, dedifferentiation, and cancer. NF-kappa B and AP-1 are necessary for basal MAT2A expression in HepG2 cells and mediate the increase in MAT2A expression in response to TNF-alpha. Up-regulation of MAT2A provides growth improvement and s-adenosylmethionine and methylthioadenosine thus can block mitogenic signaling in colon cancer cells. Lower expression of both MAT2A and MAT2beta and interfere with leptin signaling in liver cancer cells.

The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms, β, γ, ε, σ, ζ, τ and η that have been identified in mammals. The 14-3-3 epsilon, a subtype of the 14-3-3 family of proteins, was thought to be brain and neuron-specific. It has been shown to interact with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer.

Fumarase is an enzymatic factor of Krebs cycle, which catalyzes the formation of L-malate from fumarate. Fumarase exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is aimed to the mitochondrion, where the removal of the extension results in the same form as in the cytoplasm. Fumarase is similar to a number of thermostable Class-2 fumarases and functions as a homotetramer. Mutations in the Fumarase gene causes fumarase deficiency and leads to progressive encephalopathy, cerebral atrophy and developmental delay. Fumarase enzyme is also thought to act as a tumor suppressor. Leydig cell tumors are caused by Fumarase mutations and represents one of the first reports of germline mutations in any type of adult testicular tumor.

NQO1 belongs to the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. NQO1 acts as an imperative part of cellular antioxidant defense by detoxifying quinines therefore preventing the formation of reactive oxygen species. It seems that NQO1 serves as a quinone reductase relating to conjugation reactions of hydroquinons involved in detoxification pathways in addition to biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. Altered NQO1 expression is seen in many tumors and also linked to Alzheimer’s disease. NQO1 gene mutations are linked to tardive dyskinesia which is an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer.

LCAT is an extracellular cholesterol esterifying enzyme, lecithin-cholesterol acyltransferase. The esterification of cholesterol is required for cholesterol transport. LCAT is a essential enzyme in the extracellular metabolism of plasma lipoproteins.

Caspase 3 Apoptosis-Related Cysteine Peptidase (CASP3) belongs to the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a key role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to generate 2 subunits, large and small, that dimerize to create the active enzyme. CASP3 protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. CASP3 is the leading caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is linked with neuronal death in Alzheimer's disease. In addition, CASP3 is involved in the cleavage of huntingtin. CASP3 also cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. CASP3 initiates cell adhesion in sympathetic neurons through RET cleavage.

ANPEP or aminopeptidase N, is an enzyme, found in the small-intestinal and renal microvillar membrane and other plasma membranes. The enzyme has a critical part in the digestion of peptides after their hydrolysis by gastric and pancreatic proteases. ANPEP is also part ofthe processing of different peptides as well as peptide hormones, neuropeptides & chemokines. The protein takes part in angiogenesis, enhancing cholesterol crystallization &amino acid transport by formatting with SLC6A19 transport protein and regulating its activity.

17-beta-hydroxysteroid dehydrogenase 14 (HSD17B14) is a member of the 17-beta-HSD family of proteins, which regulate the availability of steroids within various tissues throughout the body. 17-beta-hydroxysteroid dehydrogenases (HSD17B14) are mainly involved in metabolism of steroids at the C17 position and also of other substrates, such as fatty acids, prostaglandins, and xenobiotics. HSD17B14 exists as a homotetramer that localizes to the cytoplasm and is highly expressed in the brain, placenta, liver and kidney.

Sepiapterin Reductase is an aldo-keto reductase that catalyzes the NADPH-dependent reduction of pteridine derivatives and is essential in the biosynthesis of BH4. Mutations in Sepiapterin Reductase gene result in DOPA-responsive dystonia due to sepiaterin reductase deficiency defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Sepiapterin reductase is part of the short-chain dehydrogenase/reductase family which reduces exogenous carbonyl compounds as well as phenylpropanedione. Sepiapterin reductase is an important enzyme for the biosynthesis of tetrahydrobiopterin, an necessary cofactor for aromatic amino acid hydrolases together with tyrosine hydroxylase, the rate-limiting enzyme in DOPA synthesis.

Adenylosuccinate lyase (ADSL) is an enzyme which converts adenylosuccinate to AMP and fumarate as part of the purine nucleotide cycle. ADSL is involved in both de novo synthesis of purines and formation of adenosine monophosphate from inosine monophosphate. ADSL catalyzes 2 reactions in AMP biosynthesis: the removal of a fumarate from succinylaminoimidazole carboxamide (SAICA) ribotide to yield aminoimidazole carboxamide ribotide (AICA) and removal of fumarate from adenylosuccinate to yield AMP. Defects in the ADSL are the cause of adenylosuccinase deficiency (ADSL deficiency). ADSL deficiency is an autosomal recessive disorder distinguished by the accumulation in the body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Adenylosuccinase deficiency results in succinylpurinemic autism, psychomotor retardation, and in some cases, growth retardation associated with muscle wasting and epilepsy.

Calnexin (CANX) belongs to the calnexin family of molecular chaperones. Calnexin is a calcium-binding, ER-associated protein that interacts briefly with newly synthesized N-linked glycoproteins, facilitating protein folding and assembly. Calnexin may also have a key role in the quality control of protein folding by retaining incorrectly folded protein subunits within the ER for degradation. Calnexin grants long-term protection of wild-type Shaker protein from ER-associated degradation. Polypeptide substrate recognition by Calnexin requires specific conformations of the Calnexin protein. Calnexin dwindles with aging and might contribute to a cytoprotection in an array of human age-related diseases.

Calpain, Small Subunit 1 (CAPNS1) belongs to the calpain small subunit family. Calpains are a ubiquitous, well-conserved family of calcium-dependent, cysteine proteases, widely distributed in mammalian cells. Calpain families are implicated in neurodegenerative processes, considering that their activation can be triggered by calcium influx and oxidative stress. Calpains function as heterodimers, comprising a specific large catalytic subunit (calpain 1 subunit in Calpain I, and calpain 2 subunit in Calpain II), and a common small regulatory subunit encoded by the CAPNS1 gene. The CAPNS1 protein is vital for the stability and function of both calpain heterodimers, whose proteolytic activities influence numerous cellular functions including apoptosis, proliferation, migration, adhesion, and autophagy.

Cathepsin-Z (CTSZ) is a lysosomal cysteine proteinase and member of the peptidase C1 family. CTSZ, which has been also known as cathepsin X and cathepsin P, exhibits carboxy-monopeptidase and carboxy-dipeptidase activities. CTSZ is expressed ubiquitously in cancer cell lines and primary tumors and, similar to other members of this family, takes part in tumorigenesis.

HMOX1 cleaves the heme ring at the alpha methene bridge to form Biliverdin. Biliverdin is then converted to Bilirubin by Biliverdin reductase. In physiological state, the highest activity of HMOX1 is found in the spleen, where senescent erythrocytes are sequestrated and destroyed. Heme Oxygenase-1 is involved in the regulation of cardiovascular function and its adaptive response to a variety of stressors. HMOX1 is induced in the colon of ulcerative colitis. HMOX1 is found to overexpress with a higher extent of intraplaque angiogenesis implies a multi-faceted role for HMOX1 in modulating the progression of atherosclerosis. HMOX1 expression reduced LPS-stimulated secretion of MCP-1, IL-6, IL-10, and TNF-alpha in murine and human macrophages.

MGMT is an enzyme that repairs O-6-methylguanine, a mutagenic DNA base damaged by endogenous and environmental alkylating agents and takes part in the cellular defense against the biological effects of O-6-methylguanine in DNA. MGMT repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. abnormal MGMT expression correlates with the prognosis in human solid cancers. MGMT decrease of expression is correlated with methylation. The human MGMT is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage. MGMT promoter hypermethylation plays an important role in the early steps of colorectal carcinogenesis. Abnormal promoter hypermethylation of MGMT gene is associated with oral squamous cell carcinomas.

Matrix Metalloproteinase-13 (MMP-13) is an enzyme that is a member of the MMP extracellular protease family. Extracellular protease enzymes, by virtue of their broad substrate specificities1, play a role in both normal and disease states of tissue proliferation. Among the targets of MMP-13 are collagen, gelatin, entactin, pro-TNF-a, and chemokine SDF-11-4.
MMP-13 is found in its latent form as a 52-56 kDa glycosylated proenzyme. Upon cleavage the 22-46 kDa5 MMP-1 becomes active in extracellular matrix remodeling.
Because of the prominent role that MMP-1 plays in cell migration and metastasis, it is an important target for inhibition screening.

Histamine N-Methyltransferase or HNMT, is located in the cell cytosol. Sadenosyl-L-methionine acts as a methyl donor for HNMT which inactivates histamine. By inactivation of histamine, it affects the immune system’s response. HNMT acts on histamine in body tissues such as kidney, central nervous system and bronchus. The protein has a crucial part in the airway response to histamine & histamine degradation process and regulation.

Elastase-2 (ELANE) is a serine protease that belongs to the chymotrypsin family. ELANE breaks down elastin, an elastic fiber together with collagen and controls the mechanical properties of connective tissue. The neutrophil form breaks down the Outer membrane protein A (OmpA) of E. coli and other Gram-negative bacteria. ELANEis inhibited by the acute-phase protein alpha 1-antitrypsin (A1AT), which binds almost irreversibly to the active site of elastase and trypsin.A1AT is usually secreted by the liver cells into the serum. A1AD leads to uninhibited destruction of elastic fiber by elastase.

AHCY is an enzyme that catalyzes the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) to adenosine (Ado) and L-homocysteine (Hcy). AHCY controls the intracellular S-adenosylhomocysteine (SAH) concentration that is crucial for transmethylation reactions. AHCY deficiency causes hypermethioninemia.