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[Congenital enzyme deficiency in carbohydrate metabolism. Its significance for clinical pediatrics and human biochemical genetics (author's transl)].

A review of the enzyme deficiencies of carbohydrate metabolism known at the present time is given. Through prominent clinical symptoms and consideration of food as a pathological agent, it is possible to suspect the various diseases before the results of the biochemical determinations are available. On account of the sometimes striking course, therapy can consequently be started at the earliest possible moment.

In Vitro Glutamine Adaptability in Murine Liver- but Not Lung-Metastasizing Triple-Negative Breast Cancer Cells.

Background: Metabolic adaptability plays a critical role in supporting the growth and survival of metastatic breast cancer cells, and potent … d glutathione synthesis. Additionally, metM-WntLiver cells utilized glucose-derived carbons through pyruvate carboxylase (PC) to maintain TCA cycle activity, with elevated PC expression and M+3-labeled oxaloacetate enrichment to a greater extent than metM-WntLung cells. PC silencing in metM-WntLiver cells enhanced cell viability under glutamine deprivation, which was …

The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice.

Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy … anied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum …

Analysis of size characterized manganese species from liver extracts using capillary zone electrophoresis coupled to inductively coupled plasma mass spectrometry (CZE-ICP-MS).

Mn is of toxicological concern because overexposure can lead to progressive, permanent neurodegenerative damage. Monomethyl-Mn-pentadienyl-t … ominantly were Mn-enzymes e.g. arginase, isocitric dehydrogenase, galactosyltransferase, prolidase, pyruvate carboxylase and oxalate oxidase. A typical Mn-transporter--Mn-albumin-- was also seen, whilst Mn-transferrin obviously was degraded during SEC separation. This Mn-compound (independent whether as a standard or from liver extract) was not stable during SEC even …

Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease.

Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D7]glucose, [13C4]β-hydroxybutyrate and [3-13C]lactate before and a

Metabolic and energy status during the dry period is crucial for the resumption of ovarian activity postpartum in dairy cows.

It is well known that the degree of negative energy balance in high-producing dairy cows is the major cause of delayed resumption of the ova … NA level (19 cows), hepatic insulin receptor decreased from dry off to early lactation, and mRNA of pyruvate carboxylase was highest at parturition and decreased in early lactation in AC only, whereas both parameters remained unchanged in OC. The mRNA abundance of phosphoenolpyruvate carboxykinase-mitochondrial increased from dry off to parturition in both groups, rem …

Proteomic and Phosphoproteomic analysis of thyroid papillary carcinoma: Identification of potential biomarkers for metastasis.

Thyroid cancer has emerged as the most rapidly proliferating solid neoplasm. In this study, we included a cohort of patients who underwent s … nthetase, 2-oxo-isovalerate dehydrogenase, succinic semialdehyde dehydrogenase, ADP/ATPtranslocase, pyruvate carboxylase, and fibrinogen. Therapeutic assays employing metformin, an AMP-activated protein kinase (AMPK) activator, alongside the phosphorylation-specific inhibitor ML-7 targeting Myosin10, demonstrated attenuated cellular proliferation, migration, and invas …

Influence of Starvation on Biochemical, Physiological, Morphological, and Transcriptional Responses Associated with Glucose and Lipid Metabolism in the Liver of Javelin Goby (Synechogobius hasta).

In this study, the influence of fasting on hepatic glucose and lipid metabolism was explored by examining biochemical, antioxidative, and morphological indicators and transcriptional expression in the liver of javelin goby (Synechogobius hasta) after 0, 3, 7, or 14 days of starvation. Marked reductions in hepatic glycogen and triglycerides occurred from the seventh day of starvation until the end of the trial (p < 0.05). However, no alterations in hepatic cholesterol or protein were detected throughout the entire experiment (p > 0.05). During fasting, the activities of pyruvate kinase, lactate

The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate-intensity exercise in human skeletal muscle.

KEY POINTS: This study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate-intensity exercise. Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2 weeks on leg substrate utilization in young and older men during two-legged dynamic knee-extensor moderate-intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise. Age and immobilization did not affect relative carbohydrate and fat utilization during exerci

Astrocyte Dysfunction in Developmental Neurometabolic Diseases.

Astrocytes play crucial roles in maintaining brain homeostasis and in orchestrating neural development, all through tightly coordinated steps that cooperate to maintain the balance needed for normal development. Here, we review the alterations in astrocyte functions that contribute to a variety of developmental neurometabolic disorders and provide additional data on the predominant role of astrocyte dysfunction in the neurometabolic neurodegenerative disease glutaric acidemia type I. Finally, we describe some of the therapeutical approaches directed to neurometabolic diseases and discuss if as

Increasing carbohydrates or nitrogenous compounds by cecal infusion leads to an opposite influence on colonic microbiota and host metabolism in a pig model.

Gut microbes, particularly those in the hindgut, play an important role in fermenting undigested nutrients (carbohydrates and proteins) and in regulating host metabolism via the gut-liver metabolic axis. However, the effects of variations in the ratio of carbohydrates to proteins on host metabolism remain largely unknown. In this study, we investigated the response of large intestinal microbiota and host metabolism to changes in nutrient substrate availability by infusing corn starch or casein hydrolysate via cecal cannulas. Twenty-four growing pigs with cecal cannulas were randomly divided in

Metabolic engineering of Komagataella phaffii for enhanced 3-hydroxypropionic acid (3-HP) production from methanol.

BACKGROUND: Bioconversion of methanol derived from CO2 reduction into value-added chemicals provides a unique approach for mitigating global … hway were overexpressed to enhance precursors availability. However, only the overexpression of the pyruvate carboxylase PYC2 gene significantly increased the 3-HP yield on biomass (YP/X) in small-scale cultivations. Co-overexpression of PYC2 and the lactate permeases ESBP6 and JEN1 genes led to a 55% improvement in 3-HP titer and product yield in methanol deep-well p …

Lack of Skeletal Muscle IL-6 Affects Pyruvate Dehydrogenase Activity at Rest and during Prolonged Exercise.

Pyruvate dehydrogenase (PDH) plays a key role in the regulation of skeletal muscle substrate utilization. IL-6 is produced in skeletal muscle during exercise in a duration dependent manner and has been reported to increase whole body fatty acid oxidation, muscle glucose uptake and decrease PDHa activity in skeletal muscle of fed mice. The aim of the present study was to examine whether muscle IL-6 contributes to exercise-induced PDH regulation in skeletal muscle. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice and floxed littermate controls (control) completed a single bout of treadmill

Buddleoside alleviates nonalcoholic steatohepatitis by targeting the AMPK-TFEB signaling pathway.

Nonalcoholic steatohepatitis (NASH) is a combination of hepatic steatosis, inflammation, and fibrosis, and it often follows simple hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). However, no pharmacological treatment is currently available for NASH. Given the important role of TFEB (transcription factor EB) in regulating the macroautophagy/autophagy-lysosomal pathway, TFEB is potentially a novel therapeutic target for treatment of NASH, which function can be regulated by AMP-activated protein kinase (AMPK) and MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1). Bud

Воздействие нового биотинового соединения в гиппокампальной ремиилизации в крысах.

Обезвоживание обычно наблюдается в нейродегенеративных расстройствах, включая множественный склероз (MS). Добавление биотина, как известно, стабилизирует прогрессирование MS. Чтобы уменьшить эффективную дозу биотина, мы синтезировали новую и превосходящую форму биотина, комплекс магния, который ионологически связан биотином (MgB), и сравнили его зависимое от дозы воздействие с биотином в одиночку после демиелинации с использованием лизолицитина (LPC) у крыс. Myelination была оценена с помощью быстрого синего пятна и иммуностаза от белка MBP, что свидетельствует о том, что наиболее значительное

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… These encouraging findings support the recent studies showing that biotin may additionally act as an essential promoter of carboxylases such as pyruvate carboxylase (PC), 3-methylcrotonyl-CoA carboxylase (MCC), propionyl-CoA carboxylase (PCC), and the two isoforms of acetyl-CoA carboxylase (ACC1 and … Biotin-Related Enzymes We assessed the effects of biotin and MgB supplementation on acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA carboxylase 2 (ACC2), pyruvate carboxylase (PC), propionyl-CoA carboxylase (PCC), 3-methylcrotonyl-CoA carboxylase (MCC). …

Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change.

The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids. To date, several molec

Autophagy in the physiological endometrium and cancer.

Autophagy is a highly conserved catabolic process and a major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles. An increasing body of evidence has unveiled autophagy as an indispensable biological function that helps to maintain normal tissue homeostasis and metabolic fitness that can also lead to severe consequences for the normal cellular functioning when altered. Recent accumulating data point to autophagy as a key player in a wide variety of physiological and pathophysiological conditions in the human endometrium, one of the most proficient self-regene

Иммунометаболизм в старении мозга и нейродегенерации: преодоление метаболических путей и иммунные ответные меры.

Сложный набор взаимодействий между иммунной системой и метаболизмом, известный как иммунометаболизм, стал критическим регулятором последствий заболеваний в центральной нервной системе. В ходе многочисленных исследований метаболические расстройства увязывались с ослабленной иммунной реакцией при старении мозга, нейродегенеративных расстройствах и травме мозга. В этом обзоре мы обсудим вопрос о том, как нарушения баланса иммунометаболизма мозга способствуют патофизиологии дисфункции мозга. В первой части обзора резюмируется вклад таких критических групп иммунной клетки, как микроглии, астроциты,

Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.

BackgroundCancer metabolism is a field focused on the unique alterations in metabolic pathways that occur in cancer cells, distinguishing them from the metabolic processes in normal cells.MethodsAn extensive review of the current literature on the metabolic adaptation of cancer cells was carried out in the current study.ResultsThe rapidly proliferating cells require high levels of molecules, such as glucose, amino acids, lipids, and nucleotides, along with increased energy demand (ATP). These requirements are met through alterations in the processes involving glucose, amino acid, lipid, and nu

Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).

Cisplatin resistance remains a primary obstacle in oncology, leading to therapeutic failure and disease recurrence. While resistance mechanisms are multifactorial, metabolic reprogramming has emerged as a critical adaptive strategy for cancer cells to evade cisplatin-induced cytotoxicity. This review synthesizes current evidence on how altered metabolism drives cisplatin resistance, with a particular emphasis on the pivotal role of pyruvate dehydrogenase kinases (PDKs). PDKs act as metabolic gatekeepers by inhibiting the pyruvate dehydrogenase complex (PDHC), diverting glucose flux away from m

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… The inhibition of PDHC activity conserves pyruvate for alternative fates, including NAD⁺ regeneration via lactate dehydrogenase, anaplerotic replenishment of oxaloacetate by pyruvate carboxylase, and transamination through alanine aminotransferase. … In parallel, pyruvate is also converted to oxaloacetate by pyruvate carboxylase, resulting in the TCA cycle [ 164 ]. In addition to pyruvate, other metabolites, such as ADP and NAD⁺, act as inhibitory signals. …