Laszlo G Boros

• MD
• Retired Professor at University of California, Los Angeles

The naturally occurring isotope of hydrogen (1H), deuterium (2H), could have an important biological role. Deuterium depleted water delays tumor progression in mice, dogs, cats and humans. Hydratase enzymes of the tricarboxylic acid (TCA) cycle control cell growth and deplete deuterium from redox cofactors, fatty acids and DNA, which undergo hydrid...

- COMMENT: The paper of Lewis et al. describes an elegant method using deuterated substrates (e.g. [3-2H]glucose or [4-2H]glucose) to trace hydrogen transfer to NADPH in the cytosol, in comparison with the same process in mitochondria. The authors nicely show a linear regression in lipogenic NADPH and (D)2-hydroxyglutarate (2HG) labeling in endogen...

Teljes önéletrajz: https://drive.google.com/open?id=1exVT7ZTzbY-kht9K-04Wj2He4W0PMNOL Dr. Boros László G. orvosi diplomáját a Szegedi Orvostudományi Egyetem Általános Orvosi Karán 1987-ben szerezte. Jelenleg egyetemi tanár, a Kalifornia Egyetem Los Angeles (UCLA) Orvosi Kar Gyermekgyógyászat Tanszékén társprofesszor, egyben anyagcsere és endokrino...

We have evaluated the biological importance of deuterium in foods based on literature data. Deuterium is a stable isotope of hydrogen that occurs naturally in our environment and is specifically enriched in certain foods. Deuterium has specific physical and chemical properties and a high kinetic isotopic effect. Morphological and physiological chan...

Introduction Large variations in fatty and amino acid natural ²H/¹H ratios in reference with solvent water point to the active involvement of compartmental, inter- and intramolecular deuterium disequilibrium in adaptive biology. Yet, the human deutenome is an untapped area of energy metabolism and health in humans. Objectives The purpose of this s...

According to the CDC, both Pfizer and Moderna COVID‐19 vaccines contain nucleoside‐modified messenger RNA (mRNA) encoding the viral spike glycoprotein of severe acute respiratory syndrome caused by corona virus (SARS‐CoV‐2), administered via intramuscular injections. Despite their worldwide use, very little is known about how nucleoside modificatio...

The HIF-1 and HIF-2 (HIF1/2) hypoxia responses are frequently upregulated in cancers, and HIF1/2 inhibitors are being developed as anticancer drugs. How could cancers resist anti-HIF1/2 therapy? We studied metabolic and molecular adaptations of HIF-1β-deficient Hepa-1c4, a hepatoma model lacking HIF1/2 signalling, which mimics a cancer treated by a...

Based on engaged experience and the recommendations of ICNIRP and the Netherlands (NL) ministry of Health, the growth and evolution to public and scientific resolutions in the domain of native and non-native electromagnetic fields (nnEMF) is easiest and most efficient when persons (schools, citizens, academics, governments) understand electromagnet...

Introduction This review addresses metabolic diversities after grain feeding of cattle using artificial total mixed ration (TMR), in place of pasture-based feeding. Objectives To determine how grain feeding impairs the deuterium-depleting functions of the anaplerotic mitochondrial matrix during milk and meat production. Methods Based on published...

In the June 11th issue of Science Advances, G. Chandramouly, et al. published an excellent article about the promiscuous reverse transcriptase function of DNA polymerase theta (Polθ; EC no. 2.7.7.7) with special emphasis on its potential DNA transforming effect also involved in cancer formation (1). A few days later the aminocoumarin antibiotic nov...

The international electromagnetic field (EMF) project of the World Health Organization (WHO) is a collaborative effort of the WHO teams for Environment, Climate Change and Health (ECCH) and Radiation and Health (ionizing and non-ionizing). The purpose of the effort is twofold. Firstly it seeks to create and house a database of legislation pertainin...

The effects of deuterium-depleted water (DDW) containing deuterium (D) at a concentration of 25 parts per million (ppm), 50 ppm, 105 ppm and the control at 150 ppm were monitored in MIA-PaCa-2 pancreatic cancer cells by the real-time cell impedance detection xCELLigence method. The data revealed that lower deuterium concentrations corresponded to l...

The 3 International Conference for Cancer Metabolism and Therapy was successfully held at the South Hospital Conference Center of Shanghai First People's Hospital, nearly 200 international experts from the field of cancer metabolism and therapy and about two thousand local scientists attended the conference. The conference was sponsored by the Yang...

The precision medicine narrative relies on the reductionist assumption that there is a strong linkage between genotype and complex traits (phenotypes). This essay uses examples from humans and other “higher” animals to argue that redundant and degenerate mechanisms operating at the physiological level limit both the general utility of this assumpti...

https://insights.ovid.com/pubmed?pmid=29702530

Besides compromising proton tunneling in H-bridges of DNA, deuterons also disrupt proton transit by the FO nanomotor in ATP synthase. This protein sits in the inner mitochondrial matrix membrane and deuterons severely compromise proton on-off loading onto the Asp61 C protein residue, which is the heart of the biological nanomotor [Aksimentiev et al...

Glucose-driven de novo serine biosynthesis contributes to metabolic stress in DNA replication defective mitochondria, which is the conclusion of Nikkanen et al., [Cell Metabolism 23, 635–648, 2016], using the elegant [U-13C6]-D-glucose single tracer metabolomics approach. Indeed, direct oxidation of glyceraldehyde 3-phosphate (GA3P; 2-hydroxy-3-oxo...

Infrared laser irradiation-induced increase in ATP production is the result of decreased interfacial water viscosity, which is the natural lubricant for nanoindentations in the rapidly turning F1 subunit of ATP synthase. On the other hand deuterium replacements in water decelerate the same process, seen as a dose dependent steep (y=-0.34x+36.1) reg...

Infrared laser irradiation-induced increase in ATP production is the result of decreased interfacial water viscosity, which lubricates nanoindentations of the rapidly turning F1 subunit of ATP synthase in the mitochondrial matrix. To the contrary, increased viscosity by deuterium replacements in water decelerates the rapidly rotating (9000 RPM) F1...

The talk is a submolecular journey with deuterium, its biochemistry and metabolomics, with potential clinical applications as the natural nuclear magnetic resonance imaging (MRI) contrast agent in disease and health. The topic is proposed for the Honors Collegium at UCLA to teach fundamental processes involved in oncoisotope chemistry, ketobolomics...

AOK-KA1632 - FOG-MAC111) - Compulsory elective subject - 2nd year medical and dentistry students - 2015/16 II. semester 2 hours lecture/week - 2 credits - Written exams - 5 graded evaluations Ref: DOI: 10.1002/anie.201405989 Exceptional Isotopic-Substitution Effect: Breakdown of Collective Proton Tunneling in Hexagonal Ice due to Partial Deuteratio...

for detailed contents of animated slides (19, 37, 38) please see supplementary material

Nutritional Ketosis - Metabolic Therapeutics - Biological Nanomechanics - Deuteriu Depletion https://youtu.be/-k002cI0Q_M?list=PL_i2ITgjpwizlwnVeGRVI_RbbsVbHsN_i [Epigenix Foundation] https://youtu.be/6P8gqB4zLGQ [UCLA - LABIOMED]

Introduction: Isocitrate dehydrogenase 1(IDH1) has been prioritized in the recent cancer biology literature because of mutations occurring in some tumor types. Additionally the wild type isoenzyme is important for metabolic reprogramming under hypoxic stress. Importantly, the role of IDH1 under other forms of metabolic stress, such as nutrient depr...

FULL CV: https://drive.google.com/open?id=1rBus-TbpwAsvRYPCIuZApZ352Tmn8sdr Dr. Boros holds a Doctor of Medicine (M.D.) degree from the Albert Szent-Györgyi School of Medicine, Szeged, Hungary. Dr. Boros is currently a Professor of Pediatrics, Endocrinology and Metabolism at the UCLA School of Medicine, investigator at the UCLA Clinical & Translati...

FULL CV: https://drive.google.com/open?id=1rBus-TbpwAsvRYPCIuZApZ352Tmn8sdr

Carbohydrates and other nutrients may carry the oncoisotope deuterium and become oncometabolites when natural carbon specific aldose-ketose transformations, i.e. isomerizations, fail to limit deuterium loading into DNA and cellular fat from deuterium depleted matrix water through metabolic hydration in mitochondria. Mitochondrial low deuterium fat...

Phosphoenolpyruvate carboxykinase (PEPCK) is well known for its role in gluconeogenesis. However, PEPCK is also a key regulator of TCA cycle flux. The TCA cycle integrates glucose, amino acid, and lipid metabolism depending on cellular needs. In addition, biosynthetic pathways crucial to tumor growth require the TCA cycle for the processing of gluc...

Natural deuteron and proton ratios influence MRI characteristics! Full talk: https://youtu.be/mRymm6gBZ10

Decreased 1H spectra spin-lattice relaxation-based 3D images of tissue water and fat using whole-body T1-weighted magnetic resonance imaging (MRI) outperform all other radiological diagnostic tools to detect cancer. A relative loss in proton signal can also be seen in egg white when compared to egg yolk using clinically applied axial MRI (Figure 1,...

Introduction: Few proteins have been found to be master-regulators of pancreatic ductal adenocarcinoma (PDA) cell metabolism (e.g., LKB1, KRAS). We recently demonstrated that the regulatory RNA binding protein, HuR, binds to numerous metabolic mRNA transcripts and regulates their expression. Additionally, HuR silencing with small interfering RNAs(s...

Most Downloaded Paper Best Publication Award by the Metabolomics Society and Springer - 2015

Sub-molecular cellular events, driven by hydrogen's replacements with deuterium, explain medical and economical failures of targeted molecular cancer drugs, which are the main conclusions of the 3 rd International Congress on Deuterium Depletion held in Budapest, Hungary, in May 2015. The Hungarian Nobel-prize winning scientist Albert Szent-Györgyi...

Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS) preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructo...

The development of obesity is becoming an international problem and the role of fructose is unclear. Studies using liver tissue and hepatocytes have contributed to the understanding of fructose metabolism. Excess fructose consumption also affects extra hepatic tissues including adipose tissue. The effects of fructose on human adipocytes are not yet...

Increased glucose decarboxylation during nucleic acid ribose synthesis occurs at the expense of glycolysis. This pathway is coupled to the recycling of drinking water, which passes through the cytoplasm after absorption. Consumption of water from the cytoplasm and cellular matrix, upon ring-opening hydrolysis in the pentose cycle, results in the pr...

The central role of hydrogen is well known in regulating chemical reaction kinetics and the role of its stable heavy isotope, deuterium (D), is also important in regulating chemical and structural protein interactions and functions. The deuterium/hydrogen (D/H) mass ratio is the largest among stable isotopes of the same element, which causes dramat...

Brasel Basic Science Conference - Tuesday, April 28, 2015 - 12:00 noon LABIOMED at the Harbor-UCLA Medical Center Impaired deuterium depletion during metabolic water production and the resulting accumulation of deuterium oxide in mitochondrial matrix and cellular fatty acid lattice induces disparities in deuterium/hydrogen ratios as a natural prot...

Impaired deuterium depletion during metabolic water production and the resulting accumulation of deuterium oxide in mitochondrial matrix and cellular fatty acid lattice induces disparities in deuterium/hydrogen ratios as a natural proton signal decreasing contrasting mechanism on 1H-NMR fat (T1) spectra-based magnetic resonance images in tumors, in...

Szent-Györgyi Albert Orvosi Centrum Biokémia összevont szeminárium II (AOK-K1632, FOG-KV111) Kötelezően választható tantárgy II. éves orvos és fogorvos hallgatók számára Kurzustípus: előadás kredit: 2 pont vizsga: beszámoló (írásbeli vizsga) (5 fokozatú jegy)

Albert Szent-Györgyi Medical University Biochemistry seminar II (AOK-KA1632, FOG-MAC111) Compulsory elective subject 2nd year medical and dentistry students 2014/15 II. semester 2 hours lecture/week

Biblical words in Genesis (First Book of Moses) refer to many chemical and physical entities, such as water, light, green plants, photosynthesis, separation of water pools by firmaments, ATP requiring muscle movements (flying, swimming), genetic inheritance carried in seeds, biological oxidation, breathing, which all can be linked with natural deut...

Regression statistics in this targeted tracer fate association study (TTFAS) is shown to reveal associations among diverse phenotypic metabolic products in fumarate hydratase-deficient UOK kidney tumor cells with defective glutaminolysis, reductive carboxylation for lipogenic citrate production, as well as the Warburg effect, using the [1,2-13C2 ]-...

Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy, that is very difficult to treat. To date, systemic treatment for PDA, either a single agent or combinations of agents, has shown only modest benefits. Numerous epidemiological studies have reported that metformin (MET), a widely used anti-diabetic drug, provides protective benefits...

Metabolomics technologies continue to develop not only to study endpoint steady-state concentrations of numerous metabolites in normal and cancer cells but also to examine metabolic flux and networks. These techniques are of importance for understanding tumor cell metabolism and for the development of new drugs and treatment strategies. The choice...

Background We are interested in mapping and understanding phenotypes that precede the development of overt signs of Huntington’s disease, in hopes of identifying pathways with the potential to be disease-modifying. Notably, the Huntington’s disease mutation is associated with early metabolic alterations of unknown aetiology in both humans and vario...

T cell activation requires increased ATP and biosynthesis to support proliferation and effector function. Most models of T cell activation are based on in vitro culture systems and posit that aerobic glycolysis is employed to meet increased energetic and biosynthetic demands. By contrast, T cells activated in vivo by alloantigens in graft-versus-ho...

Mutations in the cytosolic NADP+-dependent isocitrate dehydrogenase (IDH1) occur in several types of cancer, and altered cellular metabolism associated with IDH1 mutations presents unique therapeutic opportunities. By altering IDH1, these mutations target a critical step in reductive glutamine metabolism, the metabolic pathway that converts glutami...

Rapid tumor growth can establish metabolically stressed microenvironments that activate 5'-AMP-activated protein kinase (AMPK); a ubiquitous regulator of ATP homeostasis. Previously we investigated the importance of AMPK for the growth of experimental tumors prepared from HRAS-transformed mouse embryo fibroblasts and for primary brain tumor develop...

Numerous epidemiological studies have reported that metformin, a well-known and widely used anti-diabetic drug, may provide protective benefits in decreasing pancreatic cancer risk among the diabetic population. Following a brief introduction regarding metformin’s history and pharmacological properties, this book chapter presents epidemiological fi...

Clear cell kidney tumors become exclusively oxidative pentose cycle, hence cytoplasmic free water dependent by fumarate hydratase mutations, which disrupts the use of low deuterium containing metabolic water of the mitochondrial matrix and consumes pentose cycle-derived NADPH for reductive carboxylation [Yang Y., et al. PLoS One 8: e72179 (2013); M...

Fumarate hydratase and deuterium depletion control oncogenesis via NADPH-dependent reductive synthesis: mitochondrial matrix water, DNA deuteration and epigenetic events. ABSTRACT Clear cell kidney tumors become exclusively oxidative pentose cycle, hence cytoplasmic free water dependent by fumarate hydratase mutations, which disrupts the use of low...

Metformin, a generic glucose lowering drug, inhibits cancer growth expressly in models that employ high fat/cholesterol intake and/or low glucose availability. Here we use a targeted tracer fate association study (TTFAS) to investigate how cholesterol and metformin administration regulates glucose-derived intermediary metabolism and macromolecule s...

A variety of oncogenic and environmental factors alter tumor metabolism to serve the distinct cellular biosynthetic and bioenergetic needs present during oncogenesis. Extracellular acidosis is a common microenvironmental stress in solid tumors, but little is known about its metabolic influence, particularly when present in the absence of hypoxia. I...

Modulation of mitochondrial function through inhibiting respiratory complex I activates a key sensor of cellular energy status, the 5'-AMP-activated protein kinase (AMPK). Activation of AMPK results in the mobilization of nutrient uptake and catabolism for mitochondrial ATP generation to restore energy homeostasis. How these nutrient pathways are a...

Background: Recent observations on cancer cell metabolism indicate increased serine synthesis from glucose as a marker of poor prognosis. Expression of genes in this pathway also correlate with sensitivity to the antifolate methotrexate (Vazquez A, et al, Cancer Res. 2013 Jan 15;73(2):478-82). Using a large-scale model of human cell metabolism we h...

The present invention relates to methods and compositions for detecting immune system activation and/or the presence of an immune disorder in a patient. More particularly, methods and compositions for detecting immune system activation and/or the presence of an immune disorder in a patient by detecting, for example, the concentration of certain met...

Fumarate hydratase (FH)-deficient kidney cancer undergoes metabolic remodeling, with changes in mitochondrial respiration, glucose, and glutamine metabolism. These changes represent multiple biochemical adaptations in glucose and fatty acid metabolism that supports malignant proliferation. However, the metabolic linkages between altered mitochondri...

Includes supplementary methods, Table S1 and Figures S1-S6. Supplementary methods for the protein extraction for fumarate hydratase activity assay and for the fumarate hydratase enzyme assay protocol. Table S1, Fractional enrichment of intracellular metabolites derived from [U-13C]-glucose or [U-13C]-glutamine in FH null and restored cells. Figure...

The mechanisms by which deregulated nuclear factor erythroid-2–related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly under-stood. Using an integrated genomics and 13 C-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and mi...

The mechanisms by which deregulated nuclear factor erythroid-2-related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood. Using an integrated genomics and 13C-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and miR-...

Excess iron is associated with hepatic damage and diabetes in humans, although the detailed molecular mechanisms are not known. To investigate how iron regulates glucose homeostasis, we fed C57BL/6J male mice with high-iron (HI) diets (2 or 20 g Fe/kg chow). Mice fed an HI diet exhibited elevated AMP-activated protein kinase (AMPK) activity and imp...

Metformin, a generic glucose lowering drug, inhibits cancer growth expressly in models that employ high fat/cholesterol intake and/or low glucose availability. Here we use a targeted tracer fate association study (TTFAS) to investigate how cholesterol and metformin administration regulates glucose-derived intermediary metabolism and macromolecule s...

The rationale of this dose matching/dose escalating study was to compare a panel of flavonoids—luteolin, resveratrol, and quercetin—against the metabolite flux-controlling properties of a synthetic targeted fatty acid synthase inhibitor drug C75 on multiple macromolecule synthesis pathways in pancreatic tumor cells using [1,2-13C2]-d-glucose as the...

Background & methods: Evidence indicates that there are significant differences in how glucose and fructose affect host metabolism although the details remain unclear. We determined how liver cells adopt intermediary metabolism to fructose administration. Cultured HepG2 cells were incubated with 5 mM glucose or fructose, above the 5 mM glucose conc...

Despite the role of aerobic glycolysis in cancer, recent studies highlight the importance of the mitochondria and biosynthetic pathways as well. PPARγ coactivator 1α (PGC1α) is a key transcriptional regulator of several metabolic pathways including oxidative metabolism and lipogenesis. Initial studies suggested that PGC1α expression is reduced in t...

The lichen metabolite usnic acid (UA) has been promoted as a dietary supplement for weight loss, although cases of hepatotoxicity have been reported. Here we evaluated UA-associated hepatotoxicity in vitro using isolated rat hepatocytes. We measured cell viability and ATP content to evaluate UA induced cytotoxicity and applied (13)C isotopomer dist...

Pharmacologic contributions of directly agonizing glucagon-like peptide 1 (GLP-1) receptor or antagonizing glucagon receptor (GCGR) on energy state and glucose homeostasis were assessed in diet-induced obese (DIO) mice. Metabolic rate and respiratory quotient (RQ), hyperglycemic clamp, stable isotope-based dynamic metabolic profiling (SiDMAP) studi...

Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated...

Carbohydrate metabolism via glycolysis and the tricarboxylic acid cycle is pivotal for cancer growth, and increased refined carbohydrate consumption adversely affects cancer survival. Traditionally, glucose and fructose have been considered as interchangeable monosaccharide substrates that are similarly metabolized, and little attention has been gi...