The complexity of coffee and its impact on metabolism.

Coffee is one of the three most consumed beverages in the world. It is made by first roasting coffee beans, and then grinding and boiling or steeping the roasted beans in water (brewing). The process of roasting and brewing produces a complex mix of bioactive compounds, including methylxanthines (caffeine, theobromine, theophylline), diterpenes, chlorogenic acid, trigonelline, flavonoids, and hydroxycinnamic acid. In the body, these compounds may be metabolized to produce other bioactive compounds. For example, caffeine is primarily (80%) broken down by demethylation to produce paraxanthine. In the post-ingestion period, levels of paraxanthine may be higher than caffeine due to its slower elimination. Hence, while paraxanthine is not found in coffee itself, it has many of the same properties as caffeine and may be a major contributor to its metabolic effects. The impacts of caffeine and paraxanthine on metabolism relate to their impact on adenosine receptors (notably the A2A receptor). It has been known for almost 100 years that intake of coffee stimulates metabolism by between 5% and 20% for at least 3 h. About half of the increase in metabolic rate after drinking coffee is due to caffeine and derivatives, but the source of the other half is unclear. There are large differences in the response to the same amount of coffee in different individuals, which may be related to caffeine clearance rates, effects of other unknown pathways, genetic polymorphism, age, sex, and body composition.

Targeted metabolomics and transcript profiling of methyltransferases in three coffee species.

Coffee plants contain well-known xanthines as caffeine. Three Coffea species grown in a controlled greenhouse environment were the focus of this research. Coffea arabica and C. canephora are two first principal commercial species and commonly known as arabica and robusta, respectively. Originating in Central Africa, C. anthonyi is a novel species with small leaves. The xanthine metabolites in flower, fruit and leaf extracts were compared using both targeted and untargeted metabolomics approaches. We evaluated how the xanthine derivatives and FQA isomers relate to the expression of biosynthetic genes encoding N- and O-methyltransferases. Theobromine built up in leaves of C. anthonyi because caffeine biosynthesis was hindered in the absence of synthase gene expression. Despite this, green fruits expressed these genes and they produced caffeine. Given that C. anthonyi evolved successfully over time, these findings put into question the defensive role of caffeine in leaves. An overview of the histolocalisation of xanthines in the different flower parts of Coffea arabica was also provided. The gynoecium contained more theobromine than the flower buds or petals. This could be attributed to increased caffeine biosynthesis before fructification. The presence of theophylline and the absence of theobromine in the petals indicate that caffeine is catabolized more in the petals than in the gynoecium.

Nucleoside Phosphorylases make N7-xanthosine.

Modern, highly evolved nucleoside-processing enzymes are known to exhibit perfect regioselectivity over the glycosylation of purine nucleobases at N9. We herein report an exception to this paradigm. Wild-type nucleoside phosphorylases also furnish N7-xanthosine, a "non-native" ribosylation regioisomer of xanthosine. This unusual nucleoside possesses several atypical physicochemical properties such as redshifted absorption spectra, a high equilibrium constant of phosphorolysis and low acidity. Ultimately, the biosynthesis of this previously unknown natural product illustrates how even highly evolved, essential enzymes from primary metabolism are imperfect catalysts.

Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues.

In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.

Superoxide dismutase activity of the Salicylate-Iron complex

Background. Scavenging of superoxide radical by salicylate-iron complex was studied to determine whether or not the salicylate-iron complex was able to catalyze the dismutation of superoxide radicals, the result perhaps yielding an explanation of the antioxidant and anti-inflammatory properties of the drug. Methods. the scavenging was studied with an assay that generates Oú- 2 without the intervention of metal ions. Results. Results indicated that, in the presence of iron, salicylate was able to bring about the catalytic dismutation of the superoxide radiacal. The rate of superoxide removal was dependent on both the concentration of iron and the salicylate:iron molar ratio. Conclusions. these results may help to explain the interaction of nonsteroidal anti-inflammatory drugs with free radicals and the anti-inflammatory properties of these agents, inasmuch as accumulating evidence indicates that much of the injury observed during inflammatory disorders may be mediated by oxidative stress frequently induced by iron-dependent reactions

Xantinúria, nefrolitíase e insuficiência renal, relato de um caso / Xanthinuria, nephrolithiasis and kidney failure, a case report

Xantinúria é uma doença metabólica rara, caracterizada bioquimicamente por baixa produçäo de ácido úrico e acúmulo de xantina e hipoxantina no sangue. Como conseqüência, há uma quase ausência de ácido úrico na urina e elevada depuraçäo renal de oxipurinas. A deficiência isolada da atividade de enzima xantina oxidase é uma das causas possíveis. Cerca de 0,03 por cento dos cálculos urinários säo compostos por xantina, seja pura ou em associaçäo com ácido úrico, fosfato ou oxalato de cálcio. Descrevemos o caso de um paciente de 11 anos de idade, com insuficiência renal que formou vários cálculos urinários nos úlitmos quatro anos. Neste período o paciente apresentou infecçäo urinária recorrente e hematúria persistente. Näo havia história familiar de doença metabólica e nenhum outro membro da família havia formado cálculos renais. Uma informaçäo relevante é que os pais e os avós säo primos em primeiro grau. Os cálculos anteriormente retirados näo foram analisados. Há dois anos o paciente foi submetido a transplante renal, com boa evoluçäo clínica. Há 3 meses apresentou novos episódios de infecçäo urinária e hematúria macroscópica. Um ultrassom evidenciou atrofia bilateral dos rins remanescentes e um cálculo na bexiga, que foi retirado cirurgicamente. O cálculo analisado era de cor marrom, superfície lisa, forma oval e laminado no seu interior medindo 12 X 12 X 8 mm nos maiores diâmetros. As reaçöes para cálcio, oxalato, fosfato, magnésio, cistina, ácido úrico e amônia foram negativas. O teste para oxipurinas foi positivo.

Guanasa y metabolitos en pancreatitis isquemica experimental / Guanase and metabolites in experimental ischemic pancreatitis

El dano provocado por la pancreatitis experimental en perros, determina un aumento significativo de la actividad de la Guanasa. Este aumento se produce a las 2 hs de la isquemia en tejidos y a las 24 hs en suero. Asi mismo se determina que la actividad es similar en cabeza y cola y está ausentela actividad en el cuerpo del páncreas. Finalmente se observa que mientras las oxipurinas séricas, aumentan en forma similar a la Guanasa sérica, la Guanina sé-rica, disminuye significativamente recién a las 24 hs. Estos resultados indicanque la actividad de guanasa es un excelente "marcador" del dano pancreático en perros