Intermediary Substrates Research Articles

Hexagonal Boron Nitride as an Intermediate Layer for Gallium Nitride Epitaxial Growth in Near-Ultraviolet Light-Emitting Diodes.

We introduce the development of gallium nitride (GaN) layers by employing graphene and hexagonal boron nitride (h-BN) as intermediary substrates. This study demonstrated the successful growth of GaN with a uniformly smooth surface morphology on h-BN. In order to evaluate the crystallinity of GaN grown on h-BN, a comparison was conducted with GaN grown on a sapphire substrate. Photoluminescence spectroscopy and X-ray diffraction confirmed that the crystallinity of GaN deposited on h-BN was inferior to that of GaN grown on conventional GaN. To validate the practical applicability of the GaN layer grown on h-BN, we subsequently grew an NUV-LED structure and fabricated a device that operated well in optoelectrical performance experiments. Our findings validate the potential usefulness of h-BN to be a substrate in the direct growth of a GaN layer.

Advanced Electrodegradation of Doxorubicin in Water Using a 3-D Ti/SnO2 Anode

This study investigated the application of an advanced electrooxidation process with three-dimensional tin oxide deposited onto a titanium plate anode, named 3-D Ti/SnO2, for the degradation and mineralization of one of the most important emerging contaminants with cytostatic properties, doxorubicin (DOX). The anode was synthesized using a commercial Ti plate, with corrosion control in acidic medium, used as a substrate for SnO2 deposition by the spin-coating method. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses revealed that porous SnO2 was obtained, and the rutile phase of TiO2 was identified as an intermediary substrate onto the Ti plate. The results of CV analysis allowed us to determine the optimal operating conditions for the electrooxidation process conducted under a constant potential regime, controlled by the electron transfer or the diffusion mechanisms, involving hydroxyl radicals. The determination of UV–VIS spectra, total organic carbon (TOC), and chemical oxygen demand (COD) allowed us to identify the degradation mechanism and pathway of DOX onto the 3-D Ti/SnO2 anode. The effective degradation and mineralization of DOX contained in water by the electrooxidation process with this new 3-D dimensionally stable anode (DSA) was demonstrated in this study.

Oncometabolic Tracks in the Heart.

The term cancer and the heart is readily associated with the cardiotoxicity of antineoplastic agents, such as anthracyclines or receptor tyrosine kinase inhibitors. This Viewpoint offers a different perspective, drawing attention to the consequences of metabolic dysregulation in cancers for energy substrate metabolism and contractile function of the heart and to common cellular strategies present in cancers and in the failing heart. On the basis of his observations in proliferating ascites tumor cells, Otto Warburg1 proposed that cancer cells derive their energy from the glycolytic breakdown of glucose even in oxygen-rich conditions. Warburg postulated that this metabolic shift, or oncometabolism, arose from dysfunctional mitochondria, and the inability of cancer cells to carry out oxidative phosphorylation. The term oncometabolism refers to an ensemble of metabolic rearrangements that accompany oncogenesis and tumor progression. Recent advances in cancer cell metabolism research have amended Warburg’s seminal findings by showing, for example, that mitochondrial metabolism in cancer cells is not defective. Today’s system-oriented view is that the metabolism of cancer cells is reprogrammed to optimize the flux of glucose and amino acids into biosynthetic pathways supporting proliferation and cell division.2,3 In the context of cancer, metabolic rearrangements are required to enable tumor growth. Similar to cancer cells, cardiac metabolism is remodeled in response to stress, which allows fluxes of intermediary substrates to meet the challenges of energy demand and macromolecule synthesis. There are several lines of evidence for this hypothesis. First, the failing human heart reverts to the metabolic gene program of the fetal heart,4 which causes a shift from predominately utilization of fatty acids to glucose. Second, when stressed by pressure overload, the heart responds with an increase in glucose metabolism, as shown both ex vivo and in vivo.5 In other words, the metabolic remodeling …

Recognizing off target drug effects in the gut and brain

It is difficult to recognize off-target drug effects, leading to delays in diagnosis and predisposing patients to additional harms. Key components in the formulation of the correct diagnosis include the temporal sequence of events. The sentinel injury may target the gut and brain because of common intermediary metabolites and neuroactive substrates. The description of the complaint may vary among practitioners. The biggest issue in recognizing off target drug effects is to consider the possibility.

Peat: home to novel syntrophic species that feed acetate- and hydrogen-scavenging methanogens.

Syntrophic bacteria drive the anaerobic degradation of certain fermentation products (e.g., butyrate, ethanol, propionate) to intermediary substrates (e.g., H2, formate, acetate) that yield methane at the ecosystem level. However, little is known about the in situ activities and identities of these syntrophs in peatlands, ecosystems that produce significant quantities of methane. The consumption of butyrate, ethanol or propionate by anoxic peat slurries at 5 and 15 °C yielded methane and CO2 as the sole accumulating products, indicating that the intermediates H2, formate and acetate were scavenged effectively by syntrophic methanogenic consortia. 16S rRNA stable isotope probing identified novel species/strains of Pelobacter and Syntrophomonas that syntrophically oxidized ethanol and butyrate, respectively. Propionate was syntrophically oxidized by novel species of Syntrophobacter and Smithella, genera that use different propionate-oxidizing pathways. Taxa not known for a syntrophic metabolism may have been involved in the oxidation of butyrate (Telmatospirillum-related) and propionate (unclassified Bacteroidetes and unclassified Fibrobacteres). Gibbs free energies (ΔGs) for syntrophic oxidations of ethanol and butyrate were more favorable than ΔGs for syntrophic oxidation of propionate. As a result of the thermodynamic constraints, acetate transiently accumulated in ethanol and butyrate treatments but not in propionate treatments. Aceticlastic methanogens (Methanosarcina, Methanosaeta) appeared to outnumber hydrogenotrophic methanogens (Methanocella, Methanoregula), reinforcing the likely importance of aceticlastic methanogenesis to the overall production of methane. ΔGs for acetogenesis from H2 to CO2 approximated to -20 kJ mol(-1) when acetate concentrations were low, indicating that acetogens may have contributed to the flow of carbon and reductant towards methane.

Design and Direct Assembly of 2.5D/3D Rigid Silicon Interposer on PCB

Silicon interposer is emerging as a vehicle for integrating dies with sub 50um bump pitch in 2.5D/3D configuration. Benefits of 2.5D/3D integration are well explained in the literature, however, cost and reliability is a major concern especially with the increase in interposer size. Among the challenges, reliability issues such as warpage, cracks and thermal-stresses must be managed, in addition, multi-layer build-up flip chip substrate cost and its impact on the overall yield must be considered. Because of these challenges, 2.5D/3D silicon interposer has developed a reputation as a costly process. To overcome the reliability challenges and cost associated with typical thin interposer manufacturing and assembly, a rigid silicon interposer type structure is disclosed. In this study, interposer with thickness of greater than 300um is referred to as rigid interposer. Rigid silicon interposer is directly assembled on PCB without the need for intermediary substrate. This eliminates the need for an intermediary substrate, thin wafer handling, wafer bonding/debonding procedures and Through Silicon Via (TSV) reveal processes, thus, substantially reducing the cost of 2.5D/3D integrated products while improving reliability. A 10X10mm2 rigid silicon interposer test vehicle with 310um thickness was designed and fabricated. BGA side of the interposer with 1mm ball pitch was bumped with eutectic solder balls through a reflow process. Interposer was then assembled on a 50X50mm2 FR-4 PCB. We present design and direct assembly of the rigid silicon interposer on PCB followed by temperature cycle results using CSAM images at 250, 500, 750 and 1000 cycles. It is shown that all samples successfully passed the temperature cycle stress test.

Modeling energy and protein reserves in support of gestation and lactation: glucose as a limiting metabolite in caribou and reindeer

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The origin, global distribution, and functional impact of the human 8p23 inversion polymorphism

Genomic inversions are an increasingly recognized source of genetic variation. However, a lack of reliable high-throughput genotyping assays for these structures has precluded a full understanding of an inversion's phylogenetic, phenotypic, and population genetic properties. We characterize these properties for one of the largest polymorphic inversions in man (the ∼4.5-Mb 8p23.1 inversion), a structure that encompasses numerous signals of natural selection and disease association. We developed and validated a flexible bioinformatics tool that utilizes SNP data to enable accurate, high-throughput genotyping of the 8p23.1 inversion. This tool was applied retrospectively to diverse genome-wide data sets, revealing significant population stratification that largely follows a clinal “serial founder effect” distribution model. Phylogenetic analyses establish the inversion's ancestral origin within the Homo lineage, indicating that 8p23.1 inversion has occurred independently in the Pan lineage. The human inversion breakpoint was localized to an inverted pair of human endogenous retrovirus elements within the large, flanking low-copy repeats; experimental validation of this breakpoint confirmed these elements as the likely intermediary substrates that sponsored inversion formation. In five data sets, mRNA levels of disease-associated genes were robustly associated with inversion genotype. Moreover, a haplotype associated with systemic lupus erythematosus was restricted to the derived inversion state. We conclude that the 8p23.1 inversion is an evolutionarily dynamic structure that can now be accommodated into the understanding of human genetic and phenotypic diversity.

Competing formate- and carbon dioxide-utilizing prokaryotes in an anoxic methane-emitting fen soil.

Methanogenesis in wetlands is dependent on intermediary substrates derived from the degradation of biopolymers. Formate is one such substrate and is stimulatory to methanogenesis and acetogenesis in anoxic microcosms of soil from the fen Schlöppnerbrunnen. Formate dissimilation also yields CO(2) as a potential secondary substrate. The objective of this study was to resolve potential differences between anaerobic formate- and CO(2)-utilizing prokaryotes of this fen by stable isotope probing. Anoxic soil microcosms were pulsed daily with low concentrations of [(13)C]formate or (13)CO(2) (i.e., [(13)C]bicarbonate). Taxa were evaluated by assessment of 16S rRNA genes, mcrA (encoding the alpha-subunit of methyl-coenzyme M reductase), and fhs (encoding formyltetrahydrofolate synthetase). Methanogens, acetogens, and formate-hydrogen lyase-containing taxa appeared to compete for formate. Genes affiliated with Methanocellaceae, Methanobacteriaceae, Acetobacteraceae, and Rhodospirillaceae were (13)C enriched (i.e., labeled) in [(13)C]formate treatments, whereas genes affiliated with Methanosarcinaceae, Conexibacteraceae, and Solirubrobacteraceae were labeled in (13)CO(2) treatments. [(13)C]acetate was enriched in [(13)C]formate treatments, but labeling of known acetogenic taxa was not detected. However, several phylotypes were affiliated with acetogen-containing taxa (e.g., Sporomusa). Methanosaetaceae-affiliated methanogens appeared to participate in the consumption of acetate. Twelve and 58 family-level archaeal and bacterial 16S rRNA phylotypes, respectively, were detected, approximately half of which had no isolated representatives. Crenarchaeota constituted half of the detected archaeal 16S rRNA phylotypes. The results highlight the unresolved microbial diversity of the fen Schlöppnerbrunnen, suggest that differing taxa competed for the same substrate, and indicate that Methanocellaceae, Methanobacteriaceae, Methanosarcinaceae, and Methanosaetaceae were linked to the production of methane, but they do not clearly resolve the taxa responsible for the apparent conversion of formate to acetate.

Impaired cardiac functional reserve in type 2 diabetic db/db mice is associated with metabolic, but not structural, remodeling

To identify the nature of myocardial alterations associated with diabetes, cardiac function, structural remodeling, and gene expression in hearts of type 2 diabetic db/db mice were studied.Db/db mice showed typical characteristics of type 2 diabetes and preserved cardiac function up to 18 wks of age under non‐challenging conditions. However, β‐adrenergic stimulation with dobutamine revealed impaired contractile and relaxation reserve capacity. Tissue analyses showed no signs of structural remodeling. Neither β1‐adrenoceptor (β1AR) expression nor phosphorylation state of contractile protein targets of β1AR – protein kinase A (PKA) signaling were altered. In contrast, the substantially increased expression of uncoupling protein‐3 (UCP3) and angiopoietin‐like‐4 (Angptl4), along with decreased phosphorylation of AMP‐activated protein‐kinase (AMPK) in the heart of diabetic animals, are indicative of altered mitochondrial efficiency, decline in plasma triacylglycerol consumption and changes in intermediary substrate metabolism, respectively, which together may compromise ATP synthesis, required for maintenance of cardiac function at increased work load.We conclude that impaired cardiac functional reserve capacity during maximal β‐adrenergic stimulation, is an early sign of cardiac dysfunction in db/db mice which is primarily associated with unfavorable changes in cardiac metabolism.

V-Band Microstrip to Standard Rectangular Waveguide Transition Using a Substrate Integrated Waveguide (SIW)

In order to perform robust millimeter-wave S parameter measurements of integrated circuits, and to connect them to standard measurement equipment, a transition from microstrip to the WR 12 standard rectangular waveguide is requested. This paper proposes a new millimeter-wave microstrip to the standard WR 12 rectangular waveguide (RWG) transition by the bias of an intermediary Substrate Integrated Waveguide (SIW). The SIW technology allows wide-band and high performance circuit fabrication and enables robust transition between planar integrated circuits and standard waveguides. Commercial Finite Element Method Software, High Frequency Structure Simulator (HFSS) was used to perform the design and the optimization in term of return and insertion loss.

Regulation of redox metabolism in the mouse oocyte and embryo

Energy homeostasis of the oocyte is a crucial determinant of fertility. Following ovulation, the oocyte is exposed to the unique environment of the Fallopian tube, and this is reflected in a highly specialised biochemistry. The minute amounts of tissue available have made the physiological analysis of oocyte intermediary metabolism almost impossible. We have therefore used confocal imaging of mitochondrial and cytosolic redox state under a range of conditions to explore the oxidative metabolism of intermediary substrates. It has been known for some time that the early mouse embryo metabolises external pyruvate and lactate but not glucose to produce ATP. We now show at the level of single oocytes, that supplied glucose has no effect on the redox potential of the oocyte. Pyruvate is a cytosolic oxidant but a mitochondrial reductant, while lactate is a strong cytosolic reductant via the activity of lactate dehydrogenase. Unexpectedly, lactate-derived pyruvate appears to be diverted from mitochondrial oxidation. Our approach also reveals that the level of reduced glutathione (GSH) in the oocyte is maintained by glutathione reductase, which oxidises intracellular NADPH to reduce oxidised glutathione. Surprisingly, NADPH does not seem to be supplied by the pentose phosphate pathway in the unfertilised oocyte but rather by cytosolic NADP-dependent isocitrate dehydrogenase. Remarkably, we also found that the oxidant action of pyruvate impairs development, demonstrating the fundamental importance of redox state on early development.

The Origins of Cachexia in Acute and Chronic Inflammatory Diseases*

The term cachexia originates from the Greek root kakos hexis, which translates into "bad condition," recognized for centuries as a progressive deterioration of body habitus. Cachexia is commonly associated with a number of disease states, including acute inflammatory processes associated with critical illness and chronic inflammatory diseases, such as cancer, congestive heart failure, chronic obstructive pulmonary disease, and human immunodeficiency virus infection. Cachexia is responsible for the deaths of 10%-22% of all patients with cancer and approximately 15% of the trauma deaths that occur from sepsis-induced organ dysfunction and malnutrition days to weeks after the initial traumatic event. The abnormalities associated with cachexia include anorexia, weight loss, a preferential loss of somatic muscle and fat mass, altered hepatic glucose and lipid metabolism, and anemia. Anorexia alone cannot fully explain the development of cachexia; metabolic alterations in carbohydrate, lipid, and protein metabolism contribute to the severe tissue losses. Despite significant advances in our understanding of specific disease processes, the mechanisms leading to cachexia remain unclear and multifactorial. Although complex, increasing evidence from both animal models and clinical studies suggests that an inflammatory response, mediated in part by a dysregulated production of proinflammatory cytokines, plays a role in the genesis of cachexia, associated with both critical illness and chronic inflammatory diseases. These cytokines are further thought to induce an acute phase protein response (APR) and produce the alterations in lipid and carbohydrate metabolism identified as crucial markers of acute inflammation in states of malignancy and critical illness. Although much is still unknown about the etiology of cachexia, there is growing appreciation that cachexia represents the endproduct of an inappropriate interplay between multiple cytokines, neuropeptides, classic stress hormones, and intermediary substrate metabolism.

Glucose Uptake and Glycolysis Reduce Hypoxia-induced Apoptosis in Cultured Neonatal Rat Cardiac Myocytes

Myocardial ischemia/reperfusion is well recognized as a major cause of apoptotic or necrotic cell death. Neonatal rat cardiac myocytes are intrinsically resistant to hypoxia-induced apoptosis, suggesting a protective role of energy-generating substrates. In the present report, a model of sustained hypoxia of primary cultures of Percoll-enriched neonatal rat cardiac myocytes was used to study specifically the modulatory role of extracellular glucose and other intermediary substrates of energy metabolism (pyruvate, lactate, propionate) as well as glycolytic inhibitors (2-deoxyglucose and iodoacetate) on the induction and maintenance of apoptosis. In the absence of glucose and other substrates, hypoxia (5% CO2 and 95% N2) caused apoptosis in 14% of cardiac myocytes at 3 h and in 22% of cells at 6-8 h of hypoxia, as revealed by sarcolemmal membrane blebbing, nuclear fragmentation, and chromatin condensation (Hoechst staining), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and DNA laddering. This was accompanied by translocation of cytochrome c from the mitochondria to the cytosol and cleavage of the death substrate poly(ADP-ribose) polymerase. Cleavage of poly(ADP-ribose) polymerase and DNA laddering were prevented by preincubation with the caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-fmk) and benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone (zDEVD-fmk), indicating activation of caspases in the apoptotic process. The caspase inhibitor zDEVD-fmk also partially inhibited cytochrome c translocation. The presence of as little as 1 mM glucose, but not pyruvate, lactate, or propionate, before hypoxia prevented apoptosis. Inhibiting glycolysis by 2-deoxyglucose or iodoacetate, in the presence of glucose, reversed the protective effect of glucose. This study demonstrates that glycolysis of extracellular glucose, and not other metabolic pathways, protects cardiac myocytes from hypoxic injury and subsequent apoptosis.

An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha.

Cholesterol and its oxysterol congeners are important constituents of cell membranes and function as intermediates in several crucial biosynthetic pathways. These compounds autoregulate their metabolic fate by end-product repression and activation of downstream catabolism. Although end-product repression by oxysterols is relatively well understood, the mechanism by which these compounds act as positive transcription signalling molecules is unknown. Here we identify a specific group of endogenous oxysterols that activate transcription through the nuclear receptor LXR alpha. Transactivation of LXR alpha by oxysterols occurs at concentrations at which these compounds exist in vivo. The most potent activators also serve as intermediary substrates in the rate-limiting steps of three important metabolic pathways: steroid hormone biosynthesis, bile acid synthesis, and conversion of lanosterol to cholesterol. Our results demonstrate the existence of a nuclear receptor signalling pathway for oxysterols and suggest that LXR alpha may be important as a sensor of cholesterol metabolites.

Implantable insulin pumps and metabolic control

The development of implantable, remote-controlled insulin pumps dates back to the early 1970's when it was recognized that conventional insulin therapy may be inadequate to control microvascular complications. For the first prototypes the intraperitoneal access route was favoured because of a physiological portal/peripheral insulin gradient. With intraperitoneal insulin delivery excellent metabolic control can be obtained with glycohaemoglobin values close to the upper normal range. Although long-term studies in insulin-dependent diabetic patients show comparable results with respect to glycaemic control and intermediary substrate levels with intensive conventional therapy, the advantage of intraperitoneal insulin delivery may lie in the low rate of hypoglycaemic episodes.

Synergism of glucose and fructose in net glycogen synthesis in perfused rat livers.

Synergism of glucose and fructose in net glycogen synthesis was studied in perfused livers from 24-h fasted rats. With either glucose or fructose alone, net glycogen deposition did not occur (p greater than 0.10 for each), whereas the addition of both together resulted in significant glycogen accumulation (net glycogen accumulation was 0.21 +/- 0.03 mumol of glucose/g of liver/min at 2 mM fructose and 30 mM glucose, p less than 0.001). To better understand this synergism, intermediary substrate levels were compared at steady state with various glucose levels in the absence and in the presence of 2 mM fructose. Independent of fructose, hepatic glucose and glucose 6-phosphate increased proportionally when glucose level in the medium was raised (r = 0.86, p less than 0.001). Unlike glucose 6-phosphate, UDP-glucose did not consistently increase with glucose (p greater than 0.10); in fact, there was a small decrease at a very high glucose level (30 mM), a result consistent with the well-established activation of glycogen synthase by glucose. With elevated glucose, the level of glucose 6-phosphate was strongly correlated with glycogen content (r = 0.71, p less than 0.01, slope = 32). Adding fructose increased the "efficiency" of glucose 6-phosphate to glycogen conversion: the effect of a given increment in glucose 6-phosphate upon glycogen accumulation was increased 2.6-fold (r = 0.73, p less than 0.01, slope = 86). A kinetic modeling approach was used to investigate the mechanisms by which fructose synergized glycogen accumulation when glucose was elevated. Based on steady-state hepatic substrate levels, net hepatic glucose output, and net glycogen synthesis rate, the model estimated the rate constants of major enzymes and individual fluxes in the glycogen metabolic pathway. Modeling analysis is consistent with the following scenario: glycogen synthase is activated by glucose, whereas glucose-6-phosphatase was inhibited. In addition, the model supports the hypothesis that fructose synergizes net glycogen accumulation due to suppression of phosphorylase. Overall, our analysis suggests that glucose enhances the metabolic flux to glycogen by inducing a build up of glucose 6-phosphate via combined effects of mass action and glucose-6-phosphatase inhibition and activating glycogen synthase and that fructose enhances glycogen accumulation by retaining glycogen via phosphorylase inhibition.

Anaerobiosis in Echinochloa crus-galli (Barnyard Grass) Seedlings

Tolerance to ethanol and the ability to metabolize key intermediary substrates under anaerobiosis were studied in Echinochloa crus-galli (L.) Beauv. var oryzicola seeds to further characterize the mechanisms which enable it to germinate and grow without O(2).Our results indicate that E. crus-galli var oryzicola possesses an inherently high tolerance to ethanol and is able to metabolize low levels of ethanol in the absence of O(2). Concentrations of ethanol 45-fold greater than endogenous levels did not prove toxic to germinating seeds.Five-day anaerobically grown seedlings of E. crus-galli var oryzicola metabolized added [(14)C]sucrose primarily to CO(2) and ethanol. Of the soluble compounds labeled, the phosphorylated intermediates of glycolysis and the oxidative pentose phosphate pathway predominated more under anaerobiosis than in air. In addition, organic acids and lipids were labeled from [(14)C]sucrose, the latter indicating that metabolism of carbohydrate via acetyl-CoA occurred in the absence of O(2). Lipids were also labeled when seeds were supplied with [(14)C]ethanol or [(14)C]acetate. Labeling experiments using the above compounds plus [(14)C]NaHCO(3), showed further labeling of organic acids; succinate and citrate being labeled under nitrogen, while fumarate was formed in air.The above metabolic characteristics would allow for the maintenance of an active alcoholic fermentation system which, along with high alcohol dehydrogenase activity, would continue to recycle NAD and result in continued energy production without O(2). In addition, Echinochloa's ability to metabolize carbohydrate intermediates and to synthesize lipids indicates that mechanisms exist for providing the carbon intermediates for biosynthesis, particularly membrane synthesis for growth, even in the absence of O(2).

Activity of lactate and glucose-6-phosphate dehydrogenases in glomeruli and proximal tubules of magnesium-deficient rats.

Two groups of rats were fed respectively a magnesium-deficient and a magnesium-supplemented diet. No alteration in activity of lactate dehydrogenase in glomeruli and proximal tubules was evident in the magnesium-deficient animals after either 3 or 9 days on the diet. Activity of glucose-6-phosphate dehydrogenase increased significantly in the proximal portion of the proximal tubules after 3 days while it decreased in the distal portion of the proximal tubules after 9 days in the magnesium-deficient rats as compared to the controls. The change in activity of glucose-6-phosphate dehydrogenase in the distal portion of proximal tubules may be secondary to a redistribution of intermediary substrates into subcellular compartments.

Chlorure de lithium et biochimie du développement de l’œuf d’Amphibien

ABSTRACT The action of lithium chloride on the metabolism of carbohydrates was investigated in the amphibian Rana temporaria. Anaerobic glycolysis was inhibited in lithium-treated embryos. Lithium chloride had no action on the activity in vitro of hexokinase and aldolase, but inhibited the activity of triosephosphate-dehydrogenase. Lithium chloride inhibited the increase in oxygen consumption during embryonic development. Lithium treatment did not modify the respiratory quotient. Normal gastrulae, in the presence of intermediary substrates of carbohydrate breakdown, showed an increased oxygen consumption. This increase was slight or absent in lithium-treated gastrulae. Potassium ions compensated for the inhibition of respiration in lithium-treated gastrulae, and restored oxygen consumption to normal. Dehydrogenase activity was 25 per cent, inhibited in lithium-treated gastrulae. Lithium chloride did not affect the activity of cytochrome-oxidase. The intracytoplasmic sedimentable particulate material, mitochondria and microsomes, suffered a considerable loss of ribonucleic acid in lithium-treated gastrulae. This effect of the lithium ion on the particulate material seems to be fundamental in the development of the morphological and metabolic alterations appearing in the course of embryonic development.