Alan Crozier's research while affiliated with University of California, Davis and other places

Publications (379)

Article
A R T I C L E I N F O Keywords: Flavan-3-ols Colonic catabolic and phase II metabolism [2-14 C](−)-Epicatechin Procyanidins Theaflavins A B S T R A C T Understanding the fate of ingested polyphenols is crucial in elucidating the molecular mechanisms underlying the beneficial effects of a fruit and vegetable-based diet. This review focuses on the co...
Article
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For decades, (poly)phenols have been linked to cardiometabolic health, but population heterogeneity limits their apparent efficacy and the development of tailored, practical protocols in dietary interventions. This heterogeneity is likely determined by the existence of different metabotypes, sub-populations of individuals metabolizing some classes...
Article
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The bioavailability of apigenin and its O-glycosides in humans was investigated with apigenin-4′-glucuronide (Ap-4′-GlcUA), apigenin-7-glucuronide and apigenin-7-sulfate being identified as in vivo metabolites. Apigenin per se was poorly absorbed with metabolites equivalent to 0.5% of intake excreted in urine 0–24 h post-intake. Consumption of a pa...
Article
Scope: The study evaluated the influence of flavan-3-ol structure on the production of phenolic catabolites, principally phenyl-γ-valerolactones (PVLs) and phenylvaleric acids (PVAs). Methods and results: A set of 12 monomeric flavan-3-ols and proanthocyanidins (degree of polymerisation (DP) of 2-5), were fermented in vitro for 24 h using human...
Article
The impact of β-glucan on the bioavailability of orange juice (OJ) flavanones was investigated in a randomised controlled trial. Volunteers consumed 500 mL of OJ without or with either 3 g (OB-3) or 6 g (OB-6) of β-glucan. Urine samples, collected 12 h before and over a 0–24 h period post-supplementation, were analysed by high-performance liquid ch...
Article
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Cocoa flavanols and procyanidins (CFs), natural dietary bioactives, have been studied extensively over the past two decades for their potential health benefits. Research on their safety and efficacy is critically dependent upon on the ability to reliably characeterize the research materials that are utilized, and with growing consumer availability...
Article
Nutritional biomarkers are critical tools to objectively assess intake of nutrients and other compounds from the diet. In this context, it is essential that suitable analytical methods are available for the accurate quantification of biomarkers in large scale studies. Recently, structurally-related (-)-epicatechin metabolites (SREMs) and 5-(3',4'-d...
Preprint
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Cocoa flavanols and procyanidins (CFs),natural dietary bioactives, have been extensively studied over the past two decades. Human research on the safety and efficacy of CFs is critically dependent upon on the ability to reliably characeterize the research materials that are utilized, and with growing consumer availability of CF-based products, reli...
Article
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Diets rich in fruit and vegetables are associated with a decreased incidence of colorectal cancer (CRC) due, in part, to the bioactive (poly)phenolic components and their microbiota-mediated metabolites. This study investigated how such compounds, derived from ingested raspberries in the gastrointestinal tract, may exert protective effects by reduc...
Chapter
This chapter focuses on the occurrence of flavanones and research on their absorption, disposition, metabolism, and excretion in humans which, because of their occurrence in oranges (Citrus sinensis), has been carried out principally with orange juice where the main flavanones are the 7‐O‐rutinosides of hesperetin and naringenin. Evidence for prote...
Article
3′,4′-Dihydroxycinnamic acid (aka caffeic acid) is a common dietary component found in a variety of plant-derived food products either in a free form or esterified as in chlorogenic acids such as 5-O-caffeoylquinic acid. The dihydroxycinnamate is produced principally by hydrolysis in the colon of 5-O-caffeoylquinic acid and other caffeoylquinic aci...
Article
From a mutagenized oat population, produced by ethyl methanesulfonate mutagenesis, hulled grains from 17 lines with elevated avenanthramide (AVN) content were selected and their AVN structures, concentrations and antioxidant potentials were determined by HPLC-MS² and HPLC equipped with an on-line ABTS⁺ antioxidant detection system. The data obtaine...
Article
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There is a lack of focus on the protective health effects of phy-tochemicals in dietary guidelines. Although a number of chemical libraries and databases contain dietary phytochemicals belonging to the plant metabolome, they are not entirely relevant to human health because many constituents are extensively metabolized within the body following ing...
Article
The health benefits of orange juice (OJ) consumption are attributed in part to the circulating flavanone phase II metabolites and their microbial-derived ring fission phenolic catabolites. The present study investigated these compounds in the bloodstream after acute intake of 500 mL of OJ. Plasma samples obtained at 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24...
Article
Free download, Access your PDF reprints: https://pubs.rsc.org/en/content/authorreprints Manuscript ID: D0FO00350F Password: 626034 (this link will expire in 60 days from 26/05/2020) This study explored plasma levels and urinary and fecal excretion of metabolites and microbial-derived catabolites over a 24 h period following the ingestion of red wi...
Chapter
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The catabolism of pyrimidine nucleotides, like that of purine nucleotides, involves dephosphorylation, deamination, and glycosidic bond cleavage. However, in contrast to purine catabolism, the pyrimidine bases in most organisms are subjected to reduction rather than oxidation. Reductive pyrimidine base catabolism occurs in most microorganisms, plan...
Chapter
The de novo pyrimidine biosynthetic pathway, the synthesis of uridine‐5'‐monophosphate (UMP) from carbamoyl‐phosphate, is evolutionarily conserved from prokaryotes to eukaryotes. The pathway consists of the synthesis of carbamoyl‐aspartate, formation of orotate, and the production of UMP. In higher eukaryotes, including plants, orotate phosphoribos...
Chapter
This chapter describes the occurrence and biosynthesis of trigonelline and related nicotinate metabolites. Trigonelline is synthesized from nicotinate which is a catabolite of pyridine nucleotides. The biosynthesis of trigonelline is, therefore, analogous to that of caffeine, which is derived from purine nucleotides. Although nicotinate utilized fo...
Chapter
In plants the pyrimidine base uracil, some pyrimidine ribonucleosides and pyrimidine deoxyribonucleosides can be utilized for the generation of their respective nucleoside‐5'‐monophosphates which are then phosphorylated producing pyrimidine nucleoside‐triphosphates. Profiles of in vitro activity of enzymes involved in pyrimidine salvage have been d...
Chapter
The pathway of caffeine biosynthesis from xanthosine, a catabolite of purine nucleotides, has been elucidated in both coffee and tea. In the 1970s research on caffeine biosynthesis was carried out using intact plant tissues and tissue cultures. These studies confirmed that the purine ring of caffeine was produced from the same precursors that were...
Chapter
This chapter summarizes physiological and ecological aspects of caffeine production. There are many physiological‐based publications related to organs and tissue age, cellular and subcellular location, and control mechanisms of caffeine biosynthesis. Theobromine synthesis from purine nucleotides via xanthosine appears to be restricted to young tiss...
Chapter
A majority of the investigations on nucleotide metabolism during growth and development of plants have been carried out by monitoring the fate of radiolabelled purine and pyrimidine bases and nucleosides, which are readily taken up by tissues. Studies on pyrimidine metabolism conducted with maturing P. glauca somatic embryos demonstrated that the d...
Chapter
This chapter reviews information on the enzymes involved in the pyrimidine conversions, namely, deaminases, nucleosidases, and phosphorylases. A diversity of pyrimidine interconversions occur in different organisms. In bacteria, such as E. coli, Saccharomyces cerevisiae, and Klebsiella pneumoniae, cytosine deaminase is an enzyme in the pyrimidine i...
Chapter
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Cytokinins along with gibberellins, auxins, abscisic acid, and brassinosteroids are major classes of plant hormones. Among these naturally occurring phytohormones, cytokinins are unique in that they have an adenine‐type structure. Cytokinin biosynthesis, interconversions and degradation are involved in the regulation of cytokinin homeostasis during...
Chapter
This chapter focuses on the formation of purine, pyrimidine, and pyridine ribonucleoside monophosphates from small molecular weight precursors, the initial metabolites of de novo nucleotide biosynthesis. It also focuses on conversion of these initial metabolites to nucleoside di‐ and triphosphates, and synthesis of deoxyribonu‐cleotides from ribonu...
Chapter
This chapter describes the biosynthesis of trigonelline, and its various roles in plants, and plant biotechnology. Changes in trigonelline biosynthesis occur during the growth of leaves and fruits of coffee plants. Several in planta roles for trigonelline have been proposed, namely: as a nutrient source, a compatible solute, a bioactive substance f...
Chapter
This chapter discusses the metabolism of purine alkaloids, including biotechnology‐based studies on caffeine. In contrast to the slow metabolism of caffeine in C. arabica leaves, theophylline is catabolized very rapidly. In kucha, caffeine was metabolized to theacrine by expanding buds, and young and mature leaves; the conversion to methyluric acid...
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The de novo biosynthesis of purine nucleotides was elucidated independently by J. M. Buchanan and Greenberg in the 1950s. Substantial amounts of ureides are produced as the major nitrogen‐containing compounds derived from purine nucleotides. This chapter describes the reaction and enzymes of de novo purine nucleotide biosynthesis. There are 10 step...
Chapter
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The net formation of purine nucleotides is performed by the de novo pathway, but rapid turnover of nucleic acids, especially RNA, is required for nucleotide production by the salvage pathways. In plant cells, purine bases and nucleosides originate from the intercellular breakdown of nucleic acids and nucleotides, as well as other reactions which re...
Chapter
This chapter presents the enzymes involved in purine nucleotide biosynthesis in plants. The end products of purine catabolism in various animals differ from those found in plants. Xanthine is the starting material of purine degradation and end products in plants are ammonia, carbon dioxide, and glyoxylate. In some plant species, there is a transien...
Chapter
Four purine skeletons, namely, adenine, guanine, hypoxanthine, and xanthine occur as bases, nucleosides, and nucleotides. There is diversity in the deamination reactions in different species as they can occur at the nucleotide, nucleoside, or nucleobase levels. Dephosphorylation of purine nucleotides in plant extracts is catalysed by various enzyme...
Chapter
The chemistry of purine, pyrimidine, and pyridine nucleobases, nucleosides, and nucleotides constitute one of the oldest topics in biochemistry. This chapter describes the nomenclature and abbreviations of nucleotide‐related compounds and major chemical structures of purines, pyrimidine, and pyridine. Pyridine is a basic heterocyclic organic compou...
Chapter
Nucleotide sugars are monosaccharides that have a nucleotide, usually uridine triphosphate (UTP), bound to the carbohydrate chain through an energy rich linkage. UTP is synthesized by the de novo pyrimidine biosynthesis. Sugar nucleotides are essential building blocks for metabolism of all living organisms. In plant sugar metabolism, sugar nucleoti...
Chapter
Purines and pyrimidines are major chemical constituents of cells and occur primarily as components of DNA and RNA (polymerized nucleotides), and to a much lesser extent in the form of ‘free’ (aka ‘soluble’) nucleotides. Compared with nucleotides, free nucleosides and bases usually represent a very small fraction of the total purine and pyrimidine c...
Chapter
Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are coenzymes found in all living cells. It consists of two nucleotides, namely adenine nucleotide and a pyridine nucleotide joined through their phosphate groups. Many nucleotide reviews have described only purine and pyrimidine nucleotides without menti...
Article
All organisms produce nucleobases, nucleosides and nucleotides of purines, pyrimidines and pyridines. There have been a number of books on nucleotide metabolism in microorganisms and humans. However, this is the first to focus on plants which exhibit important differences to other organisms in key areas of nucleotide metabolism and function. The bo...
Chapter
Purine and pyrimidine metabolism, in addition to de novo biosynthesis of pyridine nucleotides, a salvage synthesis pathway also occurs. However, the pyridine ring is more efficiently recycled than is the case with degradation of purine and pyrimidine. The pyridine nucleotide cycle, which includes pyridine nucleotide catabolism and regeneration of p...
Chapter
This chapter discusses the involvement of purine and pyrimidine nucleotides in response to different types of stress. Environmental factors that affect plant growth include light, temperature, water, humidity, and nutrition. Cultured plant cells have in the main been utilized for detailed investigations on the metabolic role of nutrients. Inorganic...
Chapter
The concentration of caffeine in green coffee beans varies between 0.9‐1.3 and 1.5‐2.5% dry matter for arabica and robusta coffees, respectively. The caffeine content of beans is not markedly reduced by roasting, although losses, presumably due to sublimation, may occur if the heating process is carried out at higher temperatures. Caffeine consumpt...
Chapter
The most well‐known secondary metabolites synthesized from nucleotides are purine alkaloids. Purine alkaloids, namely methylxanthines and methylurates, occur in a variety of plant species. The major purine alkaloid typically is caffeine, which is found in popular non‐alcoholic beverages such as coffee, tea, and matĕ. The biosynthetic pathway of caf...
Article
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Flavanols and procyanidins are plant-derived bioactives that are receiving increasing attention because of their potential health benefits. Analytical tools that can accurately identify and reproducibly quantify these bioactives are critical to researchers for test material characterization, as well as to the food industry and regulators, notably f...
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Many terms for plant-derived food components are commonly used in the literature, but there is a notable lack of standardization and definition of nomenclature. The use of terms is often field-specific, leading to misunderstanding and problems with literature searches and systematic reviews, and results in isolated and divided research; this impact...
Article
Background and purpose: The pharmacology of polyphenol metabolites on β-cell function is largely undetermined. We sought to identify polyphenol metabolites that enhance the insulin-secreting function of β-cells and to explore the underlying mechanism. Experimental approach: INS-1 β-cells, rat isolated islets of Langerhans or perfused pancreas pr...
Article
Covering: 1958 to June 2018 Phenyl-γ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs) are the main metabolites of flavan-3-ols, the major class of flavonoids in the human diet. Despite their presumed importance, these gut microbiota-derived compounds have, to date, in terms of biological activity, been considered subordinate to th...
Chapter
With the recently increased accessibility of synthetic reference standards, advanced mass spectrometry platforms, and evidence from isotopically labeled ‘tracer’ and ileostomy studies, a comprehensive understanding of anthocyanin bioavailability is coming to fruition. The once general belief that anthocyanins are poorly absorbed has been disproven...
Chapter
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Primary and secondary metabolism in Coffea plants is reviewed. After a brief introduction of carbohydrate and nitrogen metabolism, the biosyntheses of three major secondary metabolites in coffee, caffeine, trigonelline and chlorogenic acids, are reviewed. Caffeine is a purine alkaloid and produced from purine nucleotides with the four-step biosynth...
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Background: Flavanols are an important class of food bioactives that can improve vascular function even in healthy subjects. Cocoa flavanols (CFs) are composed principally of the monomer (-)-epicatechin (∼20%), with a degree of polymerisation (DP) of 1 (DP1), and oligomeric procyanidins (∼80%, DP2-10). Objective: Our objective was to investigate...
Article
Epidemiologic studies suggest that diet can alter prostate cancer risk. This study aimed to establish the feasibility and acceptability of dietary modification in men at increased risk of prostate cancer. Men were invited with a PSA level of 2.0-2.95 ng/mL or 3.0-19.95 ng/mL with negative prostate biopsies. Randomization (3 × 3 factorial design) to...
Article
The present study compared and validated two analytical methods, HPLC-HRMS, and GC-MS using MSTFA as derivatization agent, for the analysis of microbiota-derived phenolic acids and aromatic compounds accumulating in urine, collected over a 24 h period after the consumption of 500 mL of orange juice. In addition, purification procedures using SDB-L...
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Observational studies indicate that the intake of polyphenol-rich foods improves vascular health, thereby significantly reducing the risk of hypertension and cardiovascular disease (CVD). Therefore, the aim of this study was to analyse the remained potential of grape by-products from important Rhône Valley red wine cultivars: Grenache, Syrah, Carig...
Article
This study developed, optimized and validated an ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) method to identify and quantify metabolites and microbial-derived catabolites in urine, plasma and feces of rats following ingestion of 50 mg of a red wine proanthocyanidin-rich extract. The method was validat...
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Plant-derived, dietary (poly)phenols have potential effects on disease-risk reduction and primary disease prevention. The characterization of (poly)phenol absorption, distribution, metabolism and excretion (ADME) is recognized as crucial step to further advance nutritional and biomedical research of these compounds; and given that (poly)phenols are...
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One of the most recently proposed candidates as a potential trigger for cardiovascular diseases is trimethylamine-N-oxide (TMAO). Possible direct effects of TMAO on myocardial tissue, independent of vascular damage, have been only partially explored so far. In the present study, we assessed the detrimental direct effects of TMAO on cardiomyocyte co...
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PurposeOrange juice (OJ) flavanones undergo limited absorption in the upper gastrointestinal tract and reach the colon where they are transformed by the microbiota prior to absorption. This study investigated the ability of two probiotic bacteria, Bifidobacterium longum R0175 and Lactobacillus rhamnosus subsp. Rhamnosus NCTC 10302 to catabolise OJ...
Article
Purine bases and nucleosides are produced by turnover of nucleotides and nucleic acids as well as from some cellular metabolic pathways. Adenosine released from the S-adenosyl-L-methionine cycle is linked to many methyltransferase reactions, such as the biosynthesis of caffeine and glycine betaine. Adenine is produced by the methionine cycles, whic...
Article
Covering: 2000 up to late 2017 This review is focussed upon the acyl-quinic acids, the most studied group within the ca. 400 chlorogenic acids so far reported. The acyl-quinic acids, the first of which was characterised in 1846, are a diverse group of plant-derived compounds produced principally through esterification of an hydroxycinnamic acid and...
Article
This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (-)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing...
Article
The incidence of overweight and obesity has reached epidemic proportions, making the control of body weight and its complications a primary health problem. Diet has long played a first-line role in preventing and managing obesity. However, beyond the obvious strategy of restricting caloric intake, growing evidence supports the specific antiobesity...
Article
The beneficial effects of consumption of berry fruits on a range of chronic diseases has been attributed (at least in part) to the presence of unique phytochemicals. Recently, we identified novel ursolic acid-based triterpenoid glycosides (TTPNs) in raspberry fruit and demonstrated their survival in human ileal fluids after feeding which confirmed...
Article
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Background: Physical exercise has been reported to increase the bioavailability of citrus flavanones.Objective: We investigated the bioavailability of orange juice (OJ) (poly)phenols in endurance-trained males before and after cessation of training for 7 d.Design: Ten fit, endurance-trained males, with a mean ± SD maximal oxygen consumption of 58.2...
Article
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Background Emerging evidence suggests that specific (poly)phenols may constitute new preventative strategies to counteract cell oxidative stress and myocardial tissue inflammation, which have a key role in the patho-physiology of diabetic cardiomyopathy. In a rat model of early diabetes, we evaluated whether in vivo administration of urolithin A (U...
Article
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Data obtained with in vitro fecal incubations and a feeding study indicate black tea theaflavin and its galloyl derivatives are not absorbed in detectable amounts in either the upper or the lower gastrointestinal tract. The theaflavin skeleton is comparatively resistant to degradation by colonic bacteria with a 67% recovery being obtained after a 2...
Article
This review considers recent investigations on the bioavailability of anthocyanins and flavanones. Both flavonoids are significant dietary components and are considered to be poorly bioavailable, as only low levels of phase II metabolites appear in the circulatory system and are excreted in urine. However, when lower molecular weight phenolic and a...
Chapter
Caffeine is a xanthine alkaloid found in non-alcoholic beverages such as tea, coffee, and cocoa. It was discovered in tea and coffee in the 1820s, but it was not until 2000 that details of molecular events associated with caffeine biosynthesis began to be unraveled. Reviewed are the occurrence of xanthine alkaloids in the plant kingdom and the eluc...
Article
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Background: Cocoa flavanol intake, especially that of (-)-epicatechin, has been linked to beneficial effects on human cardiovascular function. However, cocoa also contains the methylxanthines theobromine and caffeine, which may also affect vascular function. Objective: We sought to determine whether an interaction between cocoa flavanols and met...
Article
Ileostomy studies provide a unique insight into the digestion of foods, allowing identification of physiologically relevant dietary phytochemicals and their metabolites that are important to gut health. We previously reported an increase of components, including novel triterpenoids, in ileal fluids of 11 ileostomates following consumption of raspbe...
Article
Scope: Ileostomy studies provide a unique insight into digestion of food, allowing identification of physiologically relevant dietary phytochemicals and their metabolites important to gut health. We previously reported the consistent increase of components in ileal fluids of ileostomates after consumption of raspberries with use of non-targeted LC...
Article
Following ingestion of [2-14C](–)-epicatechin by rats, radioactivity in urine, feces, body fluids and tissues collected over a 72 h period, was measured and 14C-metabolites were analyzed by HPLC-MS2 with a radioactivity monitor. In total 78% of the ingested radioactivity was absorbed from the gastrointestinal tract (GIT), and then rapidly eliminate...
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Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of e...
Article
Orange juice is a rich source of (poly)phenols, in particular the flavanones hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside. Following the acute consumption of 500 mL of orange juice containing 398 µmol of (poly)phenols by 12 volunteers, 0-24 h plasma and urine samples were analysed by targeted high-performance liquid chromatography-high r...