Adolfo Amici

Adolfo Amici
Università Politecnica delle Marche | Università degli Studi di Ancona · Department of Odontostomatologic and Specialized Clinical Sciences (DISCO)

Biochemist

About

101
Publications
13,592
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
8,685
Citations
Citations since 2016
33 Research Items
3256 Citations
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
Introduction
The enzymes that metabolize NAD are of great interest for the understanding of certain diseases and for the development of antibacterial and anticancer drugs.
Additional affiliations
January 2004 - present
Università Politecnica delle Marche
Position
  • Professor
June 1986 - present
Università Politecnica delle Marche
Description
  • Nucleotides metabolism in human
August 1984 - June 1986
National Heart, Lung, and Blood Institute
Description
  • Chemistry of protein oxydation
Education
September 1976 - July 1983
University of Camerino
Field of study
  • Chemistry - Biological

Publications

Publications (101)
Article
The inhibition of the Epidermal Growth Factor (EGFR) represents one of the most promising strategies in non-small cell lung cancer (NSCLC) therapy. The recently identified C797S mutation causes resistance of EGFRL858R/T790M against osimertinib, the latest approved third generation EGFR inhibitor. The identification of small molecules capable of sel...
Article
Full-text available
Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) stands at a branch point of the de novo NAD ⁺ synthesis pathway and plays an important role in maintaining NAD ⁺ homeostasis. It has been recently identified as a novel therapeutic target for a wide range of diseases, including inflammatory, metabolic disorders, and aging. So far,...
Article
Full-text available
The secreted form of the enzyme nicotinamide phosphoribosyltransferase (eNAMPT), which catalyzes a key reaction in intracellular NAD biosynthesis, acts as a damage-associated molecular pattern (DAMP) triggering Toll-like receptor-4 (TLR4)-mediated inflammatory responses. However, the precise mechanism of interaction is unclear. Using an integrated...
Article
Full-text available
SARM1 is an NAD(P) glycohydrolase and TLR adapter with an essential, prodegenerative role in programmed axon death (Wallerian degeneration). Like other NAD(P)ases, it catalyzes multiple reactions that need to be fully investigated. Here, we compare these multiple activities for recombinant human SARM1, human CD38 and Aplysia californica ADP ribosyl...
Article
Full-text available
Axon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the nicotinamide adenine dinucleotide (NAD)-consuming enzyme SARM1. Here, we report a novel activator of SARM1, a metabolite of the pesticide and neurotoxin vacor. Removal of SARM1 completely re...
Article
The aim of this study was to evaluate for the first time the anti-inflammatory effects of chestnut (Castanea sativa) and Eucalyptus (Eucalyptus occidentalis) honeys collected in Italy on murine RAW 264.7 macrophages stressed with the bacterial endotoxin lipopolysaccharide (LPS). Pre-treatment with the two honeys markedly decreased apoptosis and sti...
Article
Full-text available
Colorectal cancer remains a challenging health burden worldwide. This study aimed to assess the potentiality of Strawberry tree honey (STH), a polyphenol-enriched food, to increase the effectiveness of 5-Fluorouracil (5-FU) in adenocarcinoma (HCT-116) and metastatic (LoVo) colon cancer cell lines. The combined treatment reduced cell viability and c...
Article
Full-text available
Synthetic nitrone spin-traps are being explored as therapeutic agents for the treatment of a wide range of oxidative stress-related pathologies, including but not limited to stroke, cancer, cardiovascular, and neurodegenerative diseases. In this context, increasing efforts are currently being made to the design and synthesis of new nitrone-based co...
Preprint
Full-text available
SARM1 is an NAD glycohydrolase and TLR adapter with an essential, prodegenerative role in programmed axon death (Wallerian degeneration). It has low basal NADase activity that becomes strongly activated by NAD precursor NMN. Very high levels of NAD oppose this activation, competing for the same allosteric site on SARM1′s regulatory ARM domain. Inju...
Article
Full-text available
Nicotinamide mononucleotide (NMN) is a key intermediate in the nicotinamide adenine dinucleotide (NAD+) biosynthesis. Its supplementation has demonstrated beneficial effects on several diseases. The aim of this study was to characterize NMN deamidase (PncC) inactive mutants to use as possible molecular recognition elements (MREs) for an NMN-specifi...
Article
Full-text available
Seahorses (Hippocampus spp.) are exceptional marine species considering their reproductive patterns and other features. Due to the iconic characteristics of these fishes, aquarium trade, and research efforts have increased in the last years. Consequently, novel rearing techniques have been developed; however, there is a need for improvements on a s...
Preprint
Full-text available
Axon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the nicotinamide adenine dinucleotide (NAD)-consuming enzyme SARM1 (sterile alpha and TIR motif-containing protein 1). Here, we report vacor mononucleotide (VMN), a metabolite of the pesticide a...
Article
Chemoresistance and development of relapses are ascribable to a rare cell population of tumour mass: cancer stem cells (CSCs). Targeting CSCs could increase patients' survival rate and it is important to identify molecules that can act on the main pathways of these cells. Natural bioactive compounds, of which Manuka honey (MH) is rich, could be a g...
Article
Full-text available
Elevation of Ap 4 A level in bacteria is associated with increased sensitivity to heat and oxidative stress, reduced antibiotic tolerance, and decreased pathogenicity. ApaH is the major Ap 4 A hydrolase in gamma- and betaproteobacteria and has been recently proposed as a novel target to weaken the bacterial resistance to antibiotics. Here, we ident...
Article
Full-text available
Epigallocatechin-3-gallate (EGCG) has the highest antioxidant activity compared to the others catechins of green tea. However, the beneficial effects are mainly limited by its poor membrane permeability. A derivatization strategy to increase the EGCG interaction with lipid membranes is considered as one feasible approach to expand its application i...
Poster
Familial Chylomicronemia Syndrome (FCS) is a very rare inherited disorder with extremely painful and severe, potentially fatal condition. Current therapies of FCS, like restriction of dietary fat or LipoProtein Lipase (LPL) gene therapy, have been only minimally effective. LPL is a rate-limiting enzyme that catalyzes the hydrolysis of the TriGlycer...
Article
The aim of this work was to assess the phytochemical composition and anticancer effects of Strawberry-tree honey (STH) on cellular proliferation, cell cycle and apoptosis in human colon adenocarcinoma (HCT-116) and metastatic (LoVo) cancer cells. Kaempferol and gallic acid were the major phenolic compounds. STH showed higher cytotoxic and anti-colo...
Article
The aim of the present study was to evaluate the effects of Strawberry tree honey (STH) on oxidative stress, metabolic phenotype, migration, invasion and epithelial-mesenchymal transition in adenocarcinoma (HCT-116) and metastatic (LoVo) colon cancer cells as well as in human dermal fibroblasts (HDF). Significant oxidative stress was observed throu...
Article
Electrophilic amination of diastereomeric 4‐methoxycarbonyl pyrrolidin‐2‐ones allowed to prepare both diastereomers of an amino acid bearing a quaternary chiral center, a key intermediate to antibiotic 8‐methoxyquinolone carboxylic acid. Within this synthesis, novel atropisomers, exceedingly stable at room temperature, were isolated and characteriz...
Article
Full-text available
Eukaryotic eIF5A and its bacterial orthologue EF-P are translation elongation factors whose task is to rescue ribosomes from stalling during the synthesis of proteins bearing particular sequences such as polyproline stretches. Both proteins are characterized by unique post-translational modifications, hypusination and lysinylation, respectively, wh...
Article
The redox-system is altered by oxidative stress that is initiated by oxidative agents such as lipopolysaccharides (LPS) and reactive oxygen species (ROS), which are strongly involved in chronic inflammation. Even if Manuka honey (MH) is a good source of polyphenol rich antioxidants, its antioxidant and anti-inflammatory effects are still elusive. T...
Article
The development of chemo-sensitizers is urgently needed to overcome 5-fluorouracil (5-FU) therapeutic resistance and adverse toxicity in colorectal cancer. This work aims to evaluate the synergic effects of 5-FU and Manuka honey (MH), a rich source of bioactive compounds, in enhancing the anticancer effects of this drug on human colon cancer HCT-11...
Article
Numerous investigations have been made on plant phenolic compounds and cancer prevention in recent decades. Manuka honey (MH) represents a good source of phenolic compounds such as luteolin, kaempferol, quercetin, gallic acid and syringic acid. The aim of this work was to evaluate the chemopreventive effects of MH on human colon cancer HCT-116 and...
Article
Full-text available
As a part of research project aimed to optimize antioxidant delivery, here we studied the influence of both salts and lipid matrix composition on the interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we combined in silico and experimental methods to study the ability of neutral and anionic vesicles to encapsulate EGCG in...
Article
Adenosine 5’-tetraphosphate (Ap4) is a ubiquitous metabolite involved in cell signaling in mammals. Its full physiological significance remains unknown. Here we show that two enzymes committed to NAD biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPT), can both catalyze the synthesis and degr...
Article
Background: Several species belonging to Ascomycota phylum produce extracellular ribonucleases, known as ribotoxins, which exhibit RNase activity through the cleavage of a single phosphodiester bond, located at the universally conserved sarcin/ricin loop of the large rRNA leading inhibition of protein biosynthesis. Clarifying the structure-functio...
Article
Glyoxalase II, the second of 2 enzymes in the glyoxalase system, is a hydroxyacylglutathione hydrolase that catalyses the hydrolysis of S-d-lactoylglutathione to form d-lactic acid and glutathione, which is released from the active site. The tripeptide glutathione is the major sulfhydryl antioxidant and has been shown to control several functions,...
Article
Nicotinamide riboside, the most recently discovered form of vitamin B3, and its phosphorylated form nicotinamide mononucleotide, have been shown to be potent supplements boosting intracellular nicotinamide adenine dinucleotide (NAD) levels, thus preventing or ameliorating metabolic and mitochondrial diseases in mouse models. Here we report for the...
Article
Full-text available
Starting from chiral-protected 4-hydroxymethyl pyrrolidin-2-ones, the otherwise elusive 3,4-trans-3,3,4-trisubstituted isosteres of α-methyl homoserine, tethered on a γ-lactam ring, were prepared exploiting stereoselective electrophilic aminations. These reactions led to the isolation and characterization of a novel type of atropisomers, exceedingl...
Article
Full-text available
NAD plays essential redox and non-redox roles in cell biology. In mammals, its de novo and recycling biosynthetic pathways encompass two independent branches, the "amidated" and "deamidated" routes. Here we focused on the indispensable enzymes gating these two routes, i.e. nicotinamide mononucleotide adenylyltransferase (NMNAT), which in mammals co...
Article
The redox coenzyme NAD+ is also a rate-limiting co-substrate for several enzymes that consume the molecule, thus rendering its continuous resynthesis indispensable. Due to the relevance of the NAD+-consuming reactions in complex intracellular signalling networks whose alteration leads to many disorders, NAD+ biosynthesis has emerged as a therapeuti...
Article
Novel nucleoside analogs were synthesized, in which (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol bears the nucleobase exploiting a 1-oxoethane-1,2-diyl group. Within this synthetic approach, cleavage of the N-phenylethyl group in the starting compound and introduction of the nucleobase-bearing amidic chain were accomplished with a one-pot procedure, si...
Article
Full-text available
In mammals, cellular 5'-nucleotidase (5'-NT) activity (EC 3.1.3.5) encompasses a number of genetically and structurally distinct enzyme forms, either membrane-bound or soluble, mainly cytosolic, that are characterized by broad specificity towards nucleoside 5'-monophosphate substrates differing in base (purine/pyrimidine) and/or sugar (oxy/deoxy-ri...
Article
Full-text available
A novel assay procedure has been developed to allow simultaneous activity discrimination in crude tissue extracts of the three known mammalian nicotinamide mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1) isozymes. These enzymes catalyse the same key reaction for NAD biosynthesis in different cellular compartments. The present method has been...
Data
Example of simultaneous single-sample determination of NMNAT isozyme activities in mouse tissues. (DOCX)
Data
MS Excel spreadsheet used for matrix calculation. (XLSX)
Data
Synthetic oligonucleotides used in this study. (DOCX)
Data
Composition of a typical set of discrimination assay mixtures. (DOCX)
Article
Ciliary neurotrophic factor (CNTF) is a potent survival molecule for a large number of neuronal and glial cells in culture; its expression in glial cells is strongly upregulated after a variety of nerve tissue injuries. Exogenously administered CNTF produces an anorectic effect via activation of hypothalamic neurons and stimulates neurogenesis in m...
Article
Full-text available
Cow Milk Protein Allergy (CMPA) represents the most frequent food allergy in infancy, ranging between 2 and 7.5% of the infant population. Patients with CMPA often show allergy to other foods including powdered milk containing soy or hydrolyzed proteins [1]. The milk proteins mainly responsible for the allergy are α- and β-caseins, followed by β...
Article
Full-text available
In children with Cow Milk Protein Allergy (CMPA), when it is not possible to breast feed or to use cow milk, the clinical use of donkey milk is considered since several studies have demonstrated the high similarity of donkey milk compared to human milk. An analysis was performed on donkey milk protein profile by two-dimensional electrophoresis (2-D...
Article
Full-text available
The pyridine nucleotide cycle is a network of salvage and recycling routes maintaining homeostasis of NAD(P) cofactor pool in the cell. Nicotinamide mononucleotide (NMN) deamidase (EC 3.5.1.42), one of the key enzymes of the bacterial pyridine nucleotide cycle, was originally described in Enterobacteria, but the corresponding gene eluded identifica...
Article
The living fossil Latimeria menadoensis is important to understand sarcopterygian evolution. To gain further insights into this fish species we studied its genome size, GC% and 5mC level. The genome size and the GC% of the Indonesian coelacanth seem to be very similar to those of the African coelacanth. Moreover the GC%, the CpG frequency and the 5...
Article
Nicotinate phosphoribosyltransferase (NaPRT, EC 2.4.2.11) catalyzes the conversion of nicotinate (Na) to nicotinate mononucleotide, the first reaction of the Preiss-Handler pathway for the biosynthesis of NAD(+). Even though NaPRT activity has been described to be responsible for the ability of Na to increase NAD(+) levels in human cells more effec...
Article
Melatonin is the hormonal mediator of photoperiodic information to the central nervous system in vertebrates and allows the regulation of energy homeostasis through the establishment of a proper balance between energy intake and energy expenditure. The aim of this study was to evaluate the role of melatonin in appetite central control analyzing the...
Article
The PcF protein from Phytophthora cactorum is the first member of the "PcF toxin family" from the plant pathogens Phytophthora spp. It is able to induce withering in tomato and strawberry leaves. The lack of sequence similarity with other proteins hampers the identification of the molecular mechanisms responsible for its toxicity. Here, we show tha...
Article
Full-text available
Human erythrocyte pyrimidine 5'-nucleotidase, PN-I, catalyzes the dephosphorylation of pyrimidine nucleoside monophosphates. The enzyme also possesses phosphotransferase activity, transferring phosphate groups between pyrimidine nucleoside monophosphates and various pyrimidine nucleosides. Deficiency of the enzyme activity is associated with a hemo...
Article
NAD kinase is the only known enzyme catalyzing the formation of NADP, a coenzyme implicated in most reductive biosynthetic reactions and in many antioxidant defense systems. Despite its importance, nothing is known regarding its structure or mechanism of catalysis. Mycobacterium tuberculosis NAD kinase has been overexpressed in Escherichia coli and...
Article
The enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT), a member of the nucleotidyltransferase alpha/beta phosphodiesterase superfamily, catalyzes the reaction NMN + ATP = NAD + PPi, representing the final step in the biosynthesis of NAD, a molecule playing a fundamental role as a cofactor in cellular redox reactions. NAD also serves as...
Article
This review describes the enzymes involved in human pyridine nucleotide metabolism starting with a detailed consideration of their major kinetic, molecular and structural properties. The presentation encompasses all the reactions starting from the de novo pyridine ring formation and leading to nicotinamide adenine dinucleotide (NAD(+)) synthesis an...
Article
The enzyme nicotinamide mononucleotide (NMN) adenylyltransferase (NMNAT) (EC 2.7.7.1) catalyzes the transfer of the adenylyl moiety of ATP to NMN to form NAD(+). On the basis of a remarkable structural similarity with previously described Saccharomyces cerevisiae NMNAT (yNMNAT-1), the YGR010-encoded protein was identified as a second isoform of yea...
Article
The enzyme nicotinamide mononucleotide adenylyltransferase is an ubiquitous enzyme catalyzing an essential step in NAD (NADP) biosynthetic pathway. In human cells, the nuclear enzyme, which we will now call NMNAT-1, has been the only known enzyme of this type for over 10 years. Here we describe the cloning and expression of a human cDNA encoding a...
Article
This chapter illustrates the way in which kinetic analysis provides convincing evidence for a covalent enzyme-substrate intermediate and also shows that the pyrimidine nucleotidases-I (PN-I) phosphotransferase activity displays higher affinity for oxynucleosides with respect to deoxynucleosides, whereas the contrary seems to be true for pyrimidine...
Article
Erythrocyte maturation is accompanied by RNA degradation and release of mononucleotides. Pyrimidine 5'-nucleotidase, PN-I, has been purified and characterized. The molecular and enzymatic properties determined for the enzyme shows a 36-kDa and 5.1 pI monomeric protein with no disulfide bridges and no phosphate content. The activity is dependent on...