Glutathione supplementation: An overview

This review paper aims to describe the structure, biosynthesis and function of glutathione, as well as review of its purported effects. Glutathione is one of those supplements that have piqued the interest of Filipinos because it claims to whiten the skin, as well as promising to cure a host of diseases ranging from infertility to Parkinson’s disease and even cancer. Glutathione (abbreviated GSH) is a tripeptide composed of glutamate, glycine and cysteine. It is not an essential nutrient since it can be synthesized in the body from the component amino acids found in the diet. It functions as a reducing agent (antioxidant), as well as in leukotriene synthesis and methylglyoxal detoxification. It also helps to reduce the toxicity of paracetamol by-products. Although it is not an essential nutrient, glutathione deficiency is observed in patients of some diseases such as HIV, alcoholism and liver cirrhosis. Glutathione is not effective if taken orally; thus, the effectiveness of glutathione pills is doubtful. There is a limited resource of published studies on the benefit of glutathione as a supplement to normal people. The best studies show that glutathione alleviates the side effects of chemotherapy and consequently cancer survival rate. There are no studies yet that show the effect of glutathione directly on other diseases. Glutathione appears to whiten skin by eventually reducing the formation of melanin, or at least favoring the formation of lighter melanin pigments. Its effectiveness as a topical medication (as found in soaps) is still questionable. There is still a need for more research on the administration, dosage and effects of glutathione

Utilization of Dioxygen by Carotenoid Cleavage Oxygenases

Carotenoid cleavage oxygenases (CCOs) are non-heme, Fe(II)-dependent enzymes that participate in biologically important metabolic pathways involving carotenoids and apocarotenoids, including retinoids, stilbenes, and related compounds. CCOs typically catalyze the cleavage of non-aromatic double bonds by dioxygen (O(2)) to form aldehyde or ketone products. Expressed only in vertebrates, the RPE65 sub-group of CCOs catalyzes a non-canonical reaction consisting of concerted ester cleavage and trans-cis isomerization of all-trans-retinyl esters. It remains unclear whether the former group of CCOs functions as mono- or di-oxygenases. Additionally, a potential role for O(2) in catalysis by the RPE65 group of CCOs has not been evaluated to date. Here, we investigated the pattern of oxygen incorporation into apocarotenoid products of Synechocystis apocarotenoid oxygenase. Reactions performed in the presence of (18)O-labeled water and (18)O(2) revealed an unambiguous dioxygenase pattern of O(2) incorporation into the reaction products. Substitution of Ala for Thr at position 136 of apocarotenoid oxygenase, a site predicted to govern the mono- versus dioxygenase tendency of CCOs, greatly reduced enzymatic activity without altering the dioxygenase labeling pattern. Reevaluation of the oxygen-labeling pattern of the resveratrol-cleaving CCO, NOV2, previously reported to be a monooxygenase, using a purified enzyme sample revealed that it too is a dioxygenase. We also demonstrated that bovine RPE65 is not dependent on O(2) for its cleavage/isomerase activity. In conjunction with prior research, the results of this study resolve key issues regarding the utilization of O(2) by CCOs and indicate that dioxygenase activity is a feature common among double bond-cleaving CCOs

A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Dietary -Carotene Bioavailability in Healthy Men

International audienceBACKGROUND:The bioavailability of β-carotene, the main dietary provitamin A carotenoid, varies among individuals. It is not known whether this variability can affect long-term β-carotene, and hence vitamin A, status.OBJECTIVES:We hypothesized that variations in genes involved in β-carotene absorption and postprandial metabolism could at least partially explain the high interindividual variability in β-carotene bioavailability. Thus, the main objectives of this study were to identify associated single-nucleotide polymorphisms (SNPs), and to estimate whether populations with different allele frequencies at these SNPs could have different abilities to absorb provitamin A carotenoids.METHODS:In this single-group design, 33 healthy, nonobese adult men were genotyped with the use of whole-genome microarrays. After an overnight fast, they consumed a test meal containing 100 g tomato puree providing 0.4 mg β-carotene. The postprandial plasma chylomicron β-carotene concentration was then measured at regular time intervals over 8 h. Partial least squares (PLS) regression was used to identify the best combination of SNPs in or near candidate genes (54 genes representing 2172 SNPs) that was associated with the postprandial chylomicron β-carotene response (incremental β-carotene area-under-the-curve concentration over 8 h in chylomicrons).RESULTS:The postprandial chylomicron β-carotene response was highly variable (CV = 105%) and was positively correlated with the fasting plasma β-carotene concentration (r = 0.78; P < 0.0001). A significant (P = 6.54 × 10(-3)) multivalidated PLS regression model, which included 25 SNPs in 12 genes, explained 69% of the variance in the postprandial chylomicron β-carotene response, i.e., β-carotene bioavailability.CONCLUSIONS:Interindividual variability in β-carotene bioavailability appears to be partially modulated by a combination of SNPs in 12 genes. This variability likely affects the long-term blood β-carotene status. A theoretic calculation of β-carotene bioavailability in 4 populations of the international HapMap project suggests that populations with different allele frequencies in these SNPs might exhibit a different ability to absorb dietary β-carotene. This trial was registered at clinicaltrials.gov as NCT02100774

Quantitation of retinaldehyde in small biological samples using ultrahigh-performance liquid chromatography tandem mass spectrometry

We report an ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method to quantify all-trans-retinal in biological samples of limited size (15-35mg), which is especially advantageous for use with adipose. To facilitate recovery, retinal and the internal standard 3,4-didehydroretinal were derivatized in situ into their O-ethyloximes. UHPLC resolution combined with high sensitivity and specificity of MS/MS allowed quantification of retinal-O-ethyloximes with a 5-fmol lower limit of detection and a linear range from 5fmol to 1pmol. This assay revealed that extraocular concentrations of retinal range from approximately 2 to 40pmol/g in multiple tissues-the same range as all-trans-retinoic acid. All-trans-retinoic acid has high affinity (kd⩽0.4nM) for its nuclear receptors (RARα, -β, and -γ), whereas retinal has low (if any) affinity for these receptors, making it unlikely that these retinal concentrations would activate RAR. We also show that the copious amount of vitamin A used in chow diets increases retinal in adipose depots 2- to 5-fold relative to levels in adipose of mice fed a vitamin A-sufficient diet, as recommended for laboratory rodents. This assay also is proficient for quantifying conversion of retinol into retinal in vitro and, therefore, provides an efficient method to study metabolism of retinol in vivo and in vitro