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Sirtuins are - in mammals - a family of seven enzymes (sirtuin 1-7) involved in post-translational modification of proteins (mainly deacetylation, but also: polyADP-ribosylation, demalonylation or lipoamidation), and thus - in the regulation of many metabolic processes. The activity of all sirtuins depends on the availability of NAD+. However, the function of individual isoforms is different, even mutually antagonistic. In this article the role of sirtuins in the regulation of glucose and lipid metabolism and in DNA repair mechanisms is described in detail. The significance of these enzymes in diseases pathogenesis, with particular emphasis on diabetes and cancer, is also discussed, indicating the possible therapeutic use of sirtuin activity modulators.

Aspartate aminotransferase is an organ-nonspecific enzyme located in many tissues of the human body where it catalyzes reversible reaction of transamination. There are two aspartate aminotransferase isoforms--cytoplasmic (AST1) and mitochondrial (AST2), that usually occur together and interact with each other metabolically. Both isoforms are homodimers containing highly conservative regions responsible for catalytic properties of enzyme. The common feature of all aspartate aminotransfeses is Lys - 259 residue covalent binding with prosthetic group - pyridoxal phosphate. The differences in the primary structure of AST isoforms determine their physico-chemical, kinetic and immunological properties. Because of the low concentration of L-aspartate (L-Asp) in the blood, AST is the only enzyme, which supply of this amino acid as a substrate for many metabolic processes, such as urea cycle or purine and pyrimidine nucleotides in the liver, synthesis of L-arginine in the kidney and purine nucleotide cycle in the brain and the skeletal muscle. AST is also involved in D-aspartate production that regulates the metabolic activity at the auto-, para- and endocrine level. Aspartate aminotransferase is a part of the malate-aspartate shuttle in the myocardium, is involved in gluconeogenesis in the liver and kidney, glyceroneogenesis in the adipose tissue, and synthesis of neurotransmitters and neuro-glial pathway in the brain. Recently, the significant role of AST in glutaminolysis - normal metabolic pathway in tumor cells, was demonstrated. The article is devoted the role of AST, known primarily as a diagnostic liver enzyme, in metabolism of various human tissues and organs.

The CEA related cell adhesion molecules (CEACAM) contain variable and constant immunoglobulin-like domains and are classified as a member of the immunoglobulin supergene family, IgSF. The seven CEACAM (CD66) antigens (CEACAM1, CEACAM3, CEACAM4, CEA, CEACAM6, CEACAM7 and CEACAM8) differ in the number of Ig-like domains, sugar content, presence of isoforms, tissue distribution and form of membrane attachment (transmembrane region or GPI anchor). CEACAMs with a transmembrane region possess a cytoplasmic domain with or without the immunoreceptor motifs. The structural diversity of CEACAMs results in their multifunctionality, especially displayed in calcium independent homo- and heterotypic adhesion interactions. The scientific data, collected mainly for CEA, strongly confirm involvement of this molecule in colorectal cancer. Recent research also indicates that CEACAMs play an important role in signal transduction, recognition and binding of pathogenic bacteria belonging to Neisseria and Escherichia genera.

The article presents the melanogenesis pathway and the role of cyclic adenosine monophosphate (cAMP) and microphthalmia transcription factor (MITF) in regulation of this process. Products of melanogenesis are eu- and/or pheomelanins synthesized in a multistage process of tyrosine oxidation and polymerization. The conversions require the presence of tyrosinase (TYR, key enzyme), tyrosine hydroxylase isoform I (THI) and tyrosinase related proteins (TRP1 and TRP2). Many types of signal molecules and transcription factors participate in regulation of melanin synthesis, but the most important are cAMP and MITF. cAMP is the second messenger in the intracellular signal cascade, which is synthesized from adenosine triphosphate (ATP) by adenylyl cyclase, activated among others by the melanocortin receptor and the αS subunit of G protein. The signal molecule cAMP regulates MITF, TYR, THI, GTP-cyclohydroxylase I (GTP-CHI) transcription and phenylalanine hydroxylase (PAH) phosphorylation at Ser16 by protein kinase A (PKA). Mutations of genes encoding proteins belonging to the cAMP signal cascade may lead to McCune-Albright and Carney syndromes. MITF is one of the most important nuclear transcription factors regulating melanogenesis. Currently 10 isoforms of human MITF are known, but in melanocytes only MITF-M, MITF-Mdel, MITF-A and MITF-H occur. MITF transcription factor regulates melanogenesis by activation of tyrosinase, TRP1 and TRP2 transcription. It also affects expression of other factors regulating melanosome maturation, biogenesis and transport. Moreover, it regulates melanocyte proliferation and protection against apoptosis. Mutations of the MITF gene may lead to hereditary diseases: Waardenburg type II and Tietz syndromes.

Lamins belong to type V intermediate filaments superfamily. They are the main structural constituencies of the nuclear lamina but they also influence on chromatin structure, regulation of gene expression, localization and probably protein degradation. Because lamins play many different roles within the cell, mutations in their genes can results in variety of pathological phenotypes. Mutations in LMNA gene are the cause of many different diseases, called laminopathies. Among laminopathies are muscle tissue diseases, adipose tissue diseases and also progerias, the premature aging syndromes. One of the progerias, which results from mutation in LMNA gene, is Hutchinson-Gilford progeria syndrome (HGPS). It seems that the same molecular mechanisms which are responsible for premature aging of cells of HGPS patients, are involved in physiological aging.

The 14-3-3 proteins are a family of highly conserved proteins found in all eukaryotes - from the yeasts to mammals. They regulate several cellular processes recognizing unique conservative, mostly phosphorylated motif of partner proteins. Binding of the 14-3-3 proteins regulates their partners through a variety of mechanisms, such as altering their catalytic activity, subcellular localization, stability or altering their interactions with other protein molecules. The native 14-3-3 proteins are present in form of homo- and hetero-dimers. The most structurally variable N-and C-termini are responsible for isoform specific protein-protein interactions, and cellular localization. In plant cell, 14-3-3 proteins appear to play an important role in regulation of key enzymes of carbon and nitrogen metabolism, modulation ion pumps and channels. They are also involved in signal transduction pathways and even in gene expression.

Affectivity of activity of wild-type estrogen receptors forms depends not only from transcriptional activity of their encoding genes, but also from participation of ERs isoforms in entire ERs mRNA pool. Estrogen receptor mRNA isoforms are essential intracellular factor regulating cellular answer of estrogen. ERs expression, as well as the mRNA splice variants, may influence the biological properties of some tumors and affect their ability to respond to estrogen and antiestrogen therapies. The aim of the study was qualitative and quantitative analysis and comparison of mRNA ER-alpha and their isoforms concentration profile in endometrial adenocarcinoma and normal endometrium as control group. The level of ER-alpha mRNA was estimated using RT-QPCR method in proliferative phase (n = 12) and endometrial adenocarcinoma (n = 15). Types of alternative mRNA ER-alpha splice variants were marked. Seven transcripts ER-alpha (ER-alpha/delta 2, ER-alpha/3, ER-alpha/delta 2-3, ER-alpha 4-ER-alpha/delta 7) were quantitatively evaluated. Proportional analysis of particular mRNA ER-alpha isoforms participation in entire pool of mRNA ER-alpha showed diminution of ER-alpha/delta 2, ER-alpha/delta 2-3, ER-alpha/delta 7 what correlated with simultaneous decrease of mRNA copy number in endometrial adenocarcinoma. Endometrial adenocarcinoma was also characterized by presence of isoforms not stepping out in investigated segments of normal endometrium: ER-alpha/delta 4, ER-alpha/delta 6 and ER-alpha/delta 5 being with factor about high transcriptional activity potential, are able to activate transcription of estrogen receptors target genes independently from ligad binding. Additional ER-alpha isoforms appearing in endometrial adenocarcinoma instead of wild-type ER? proves, that in chance of tumor transformation the number of potranscriptional modifications increases. One can not exclude that their number is connected with genetic changes starting carcinogenesis in endometrium. Changes of mRNA ER-alpha copy number and presence of definite isoforms may altered of signaling estrogen pathways.