A carnitina, L-carnitina ou levocarnitina é um composto quaternário de amónio envolvido no metabolismo da maior parte dos mamíferos, plantas e algumas bactérias. Encontrada em quase todas as células do organismo, atua na geração de energia (ATP), a partir de ácidos graxos (gordura). Ela ajuda a melhorar os níveis de colesterol bom (HDL) melhorando o funcionamento do coração e da circulação sanguínea.
Introdução
O que você precisa saber de cara
Doença rara que afeta a metabolização de gorduras nas mitocôndrias, levando a quadros de encefalopatia aguda, acidose metabólica e atraso no desenvolvimento. Pode manifestar-se com insuficiência respiratória, problemas cardíacos e renais, além de alterações visuais.
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 104 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 273 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
Triagem neonatal (Teste do Pezinho)
A triagem neonatal permite diagnóstico precoce e início imediato do tratamento.
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
15 genes identificados com associação a esta condição.
Facilitates flavin adenine dinucleotide (FAD) translocation across the mitochondrial inner membrane into the mitochondrial matrix where it acts as a redox cofactor to assist flavoenzyme activities in fundamental metabolic processes including fatty acid beta-oxidation, amino acid and choline metabolism as well as mitochondrial electron transportation. In particular, provides FAD to DLD dehydrogenase of the glycine cleavage system, part of mitochondrial one-carbon metabolic pathway involved in neu
Mitochondrion inner membrane
Exercise intolerance, riboflavin-responsive
A riboflavin-responsive form of exercise intolerance, a condition characterized by failure to maintain an expected level of force during sustained or repeated muscle contraction, resulting in an overwhelming sense of tiredness, lack of energy and feeling of exhaustion. RREI transmission pattern is consistent with autosomal recessive inheritance.
Accepts electrons from ETF and reduces ubiquinone
Mitochondrion inner membrane
Glutaric aciduria 2C
An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, PubMed:33124720). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal e
Cell membraneApical cell membraneBasal cell membraneEndoplasmic reticulum
Systemic primary carnitine deficiency
Autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. Present early in life with hypoketotic hypoglycemia and acute metabolic decompensation, or later in life with skeletal myopathy or cardiomyopathy.
Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (PubMed:17564966, PubMed:18227065, PubMed:7668252, PubMed:9461620, PubMed:9599005, PubMed:9839948). The first step of FAO consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transf
Mitochondrion inner membrane
Acyl-CoA dehydrogenase very long-chain deficiency
An inborn error of mitochondrial fatty acid beta-oxidation which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form characterized by early onset, high mortality and high incidence of cardiomyopathy; a milder childhood form with later onset, characterized by hypoketotic hypoglycemia, low mortality and rare cardiomyopathy; an adult form, with isolated skeletal muscle involvement, rhabdomyolysis and myoglobinuria, usually triggered by exercise or fasting.
Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate
Mitochondrion
3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency
A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly.
Mitochondrial fatty acid beta-oxidation enzyme that catalyzes the third step of the beta-oxidation cycle for medium and short-chain 3-hydroxy fatty acyl-CoAs (C4 to C10) (PubMed:10231530, PubMed:11489939, PubMed:16725361). Plays a role in the control of insulin secretion by inhibiting the activation of glutamate dehydrogenase 1 (GLUD1), an enzyme that has an important role in regulating amino acid-induced insulin secretion (By similarity). Plays a role in the maintenance of normal spermatogenesi
Mitochondrion matrix
3-alpha-hydroxyacyl-CoA dehydrogenase deficiency
An autosomal recessive, metabolic disorder with various clinical presentations including hypoglycemia, hepatoencephalopathy, myopathy or cardiomyopathy, and in some cases sudden death.
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. Terminal step in leucine catabolism. Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism
Mitochondrion matrixPeroxisome
3-hydroxy-3-methylglutaryl-CoA lyase deficiency
An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.
Medium-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (PubMed:1970566, PubMed:21237683, PubMed:2251268, PubMed:8823175). The first step of FAO consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physi
Mitochondrion matrix
Acyl-CoA dehydrogenase medium-chain deficiency
An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy.
This enzyme has two activities: FAD diphosphatase activity and FAD synthase activity (PubMed:16643857, PubMed:21924249, PubMed:21951714, PubMed:23443125, PubMed:25135855, PubMed:26277395, PubMed:27259049, PubMed:31351152, PubMed:38688286). FAD diphosphatase acts on FAD and NADH to produce FMN and NMNH(2-), respectively (PubMed:26277395, PubMed:31351152, PubMed:38688286). FAD synthase catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme (PubM
NucleusMitochondrion matrixCytoplasm, cytosol
Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency
An autosomal recessive, inborn error of metabolism characterized by variable mitochondrial dysfunction. Clinical features range from severe cardiac and respiratory insufficiency with onset in infancy and resulting in early death, to mild muscle weakness with onset in adulthood. Some patients show significant improvement with riboflavin treatment. Analysis of skeletal muscle show multiple mitochondrial respiratory chain deficiency and a lipid storage myopathy in most patients.
Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:1550553, PubMed:29915090, PubMed:30850536, PubMed:8135828, PubMed:31604922). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specific
MitochondrionMitochondrion inner membrane
Mitochondrial trifunctional protein deficiency 1
An autosomal recessive metabolic disorder of long-chain fatty acid oxidation, biochemically characterized by loss of all enzyme activities of the mitochondrial trifunctional protein complex. The disease phenotype ranges from a fatal form characterized by early-onset cardiomyopathy, cardiac failure and early death to less severe, late-onset forms with myopathy, recurrent rhabdomyolysis, and sensorimotor axonal neuropathy as key features.
Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:15159392, PubMed:15975918, PubMed:25416781). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (Probable). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:7912128). ETFB binds an AMP mo
Mitochondrion matrix
Glutaric aciduria 2B
An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.
Mediates the electroneutral exchange of acylcarnitines (O-acyl-(R)-carnitine or L-acylcarnitine) of different acyl chain lengths (ranging from O-acetyl-(R)-carnitine to long-chain O-acyl-(R)-carnitines) with free carnitine ((R)-carnitine or L-carnitine) across the mitochondrial inner membrane, via a ping-pong mechanism (Probable) (PubMed:12892634, PubMed:18307102). Key player in the mitochondrial oxidation pathway, it translocates the fatty acids in the form of acylcarnitines into the mitochondr
Mitochondrion inner membrane
Carnitine-acylcarnitine translocase deficiency
A rare long-chain fatty acid oxidation disorder. Metabolic consequences include hypoketotic hypoglycemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical features include neurologic abnormalities, cardiomyopathy, arrhythmias, skeletal muscle damage, liver dysfunction and episodes of life-threatening coma, which eventually lead to death. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate.
Short-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (By similarity). The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (By similarity). Among
Mitochondrion matrix
Acyl-CoA dehydrogenase short-chain deficiency
An inborn error of mitochondrial fatty acid beta-oxidation resulting in acute acidosis and muscle weakness in infants, and a form of lipid-storage myopathy in adults.
Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:10356313, PubMed:15159392, PubMed:15975918, PubMed:27499296, PubMed:9334218). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (PubMed:9334218). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabol
Mitochondrion matrix
Glutaric aciduria 2A
An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.
Together with NDUFAF1 and ECSIT, forms part of the mitochondrial complex I (MCIA),which is required for the biogenesis of respiratory Complex I (CI) and is therefore crucial for the activation of the oxidative phosphorylation system (PubMed:20816094, PubMed:24158852, PubMed:32320651, PubMed:38086790). ECSIT binding triggers a large conformational change, switching ACAD9 from a fatty acid oxidation (FAO) enzyme to a CI assembly factor (PubMed:38086790). The function in CI assembly is independent
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 20
An autosomal recessive metabolic disorder associated with mitochondrial complex I deficiency, resulting in multisystemic and variable manifestations. Clinical features include infantile onset of acute metabolic acidosis, Reye-like episodes (brain edema and vomiting that may rapidly progress to seizures, coma and death), exercise intolerance, hypertrophic cardiomyopathy, liver failure, muscle weakness, and neurologic dysfunction.
Variantes genéticas (ClinVar)
891 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
22 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Alteração da oxidação do ácido graxo mitocondrial
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Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Distinct effects of ketogenic and non-ketogenic weight-loss diets on hepatic steatosis and mitochondrial metabolism in MASLD.
Weight loss is the cornerstone of therapy for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the optimal dietary approach for reducing intrahepatic triglycerides (IHTG) and the mechanisms underlying steatosis resolution remain poorly defined. We investigated whether weight loss via a ketogenic diet (KD) compared with a non-ketogenic diet (ND) differentially affects IHTG content, hepatic mitochondrial metabolism, and the circulating metabolome. Individuals with varying IHTG content underwent short-term hypocaloric KD and ND in a crossover design. Before and after each diet, IHTG was quantified by proton magnetic resonance spectroscopy and liver stiffness by magnetic resonance elastography. We used state-of-the-art isotope tracer methodology to compare in vivo rates of hepatic mitochondrial tricarboxylic acid (TCA) cycle oxidation, endogenous glucose production, and β-hydroxybutyrate production (ketogenesis). Targeted plasma metabolomics by NMR and LC-MS was used to evaluate systemic metabolic responses. Despite similar energy deficits and body fat loss, IHTG decreased 45% more with KD than ND (-29% vs. -20%), accompanied by a threefold greater improvement in hepatic insulin sensitivity (59% vs. 21%). KD, but not ND, markedly reduced serum insulin concentrations (-54%), thereby promoting lipolysis and intrahepatic fatty acid partitioning toward mitochondrial β-oxidation, increasing hepatic mitochondrial [NADH]/[NAD+] (redox state) (+51%), and decreasing rates of hepatic mitochondrial TCA cycle oxidation (-34%). KD, but not ND, increased plasma concentrations of branched-chain amino acids, acylcarnitines, and TCA cycle intermediates. Both diets ameliorated MASLD, but KD produced a greater reduction in IHTG owing to a starvation-like metabolic state. However, the benefits of KD were accompanied by increased hepatic mitochondrial redox state and suppression of TCA cycle oxidation, which are features previously linked to progressive liver injury. This study provides mechanistic justification for considering dietary composition, in addition to caloric restriction, as a key determinant of steatosis resolution in metabolic dysfunction-associated steatotic liver disease (MASLD). The findings highlight a potential trade-off between greater short-term reductions in liver fat and the emergence of metabolic features previously associated with increased susceptibility to liver injury. While a ketogenic diet may facilitate rapid liver fat reduction in selected clinical contexts, its use should be approached cautiously, particularly in individuals with advanced MASLD. These results underscore the need for systematic evaluation of dietary composition as a determinant of both efficacy and safety of nutritional interventions for MASLD. NCT03737071.
Renal Ketogenesis Protects Against Ischemic Kidney Injury.
Proximal tubular expression of hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) during ischemic injury increases kidney ketone and prostaglandin content. Kidney HMGCS2 deficiency emerged as both a biomarker and contributor to kidney disease. Renal ketogenesis supported the maintenance of proximal tubular fatty acid oxidation. Abnormal renal fatty acid oxidation in kidney disease suggests that dysregulated metabolism is a key component of kidney disease pathogenesis. While the liver is the main ketogenic organ, the rate-limiting enzyme for ketogenesis, mitochondrial hydroxymethylglutaryl-CoA synthase 2 (HMGCS2), is induced in the proximal tubule of the kidney during fasting. We previously demonstrated that HMGCS2 induced in the kidney does not contribute to the circulating pool of ketones during fasting and cannot compensate for hepatic ketogenic deficiency. We hypothesized that kidney HMGCS2 may be acting locally within the kidney to maintain normal function during metabolic stress or injury. Mice with kidney- or liver-specific deletion of Hmgcs2 were subjected to ischemia/reperfusion injury (IRI). Kidney histology, metabolomics, and lipidomics were analyzed. Mice were placed on a ketogenic diet for 4 days to increase plasma and kidney ketone content. Using novel mouse models with proximal tubular hemagglutinin-tagged mitochondria with or without Hmgcs2 deletion, proximal tubular-specific mitochondria were isolated, and fatty acid oxidation capacity was measured after IRI. Mice with kidney-specific Hmgcs2 deletion had significantly more kidney injury after IRI compared with wild-type controls. Kidneys lacking HMGCS2 exhibited a decrease in ketone content and an increase in lipid droplet accumulation after IRI. Proximal tubular-specific mitochondria lacking HMGCS2 had significantly lower fatty acid oxidation capacity both at baseline and after ischemic injury. Administration of a ketogenic diet for 4 days before IRI was sufficient to decrease kidney injury and augment mitochondrial fatty acid oxidation in kidney Hmgcs2 knockout mice. Kidney tissue lipidomics revealed that the loss of kidney HMGCS2 was associated with a decrease in both arachidonic acid containing phospholipids and prostaglandin levels. Loss of renal HMGCS2 and resultant ketogenesis increased ischemia-induced injury and decreased mitochondrial fatty acid oxidation capacity, suggesting a role in renal ketogenesis in limiting AKI. The primary energy source shifts from glucose to fat during periods of fasting or starvation, when carbohydrate intake is markedly reduced. Adipose tissue releases stored triglycerides, which are hydrolyzed into free fatty acids (FFAs) and glycerol. FFAs are transported to the liver, where they undergo β-oxidation, generating large amounts of acetyl-CoA. Accumulation occurs when acetyl-CoA production exceeds the liver’s oxidative capacity in the citric acid cycle. This imbalance is partly driven by decreased availability of oxaloacetate, which is diverted toward gluconeogenesis. Excess acetyl-CoA cannot be fully oxidized or redirected into fatty acid synthesis. The metabolic bottleneck channels acetyl-CoA into ketogenesis, in which the liver converts acetyl-CoA into ketone bodies, primarily acetoacetate and β-hydroxybutyrate (see Image. Ketogenesis Pathway). Ketone bodies are released into the circulation and serve as an alternative energy substrate for peripheral tissues, particularly the brain, during prolonged carbohydrate deficiency. Plasma concentrations rise when the rate of ketone body production surpasses peripheral utilization, resulting in ketonemia. Progressive accumulation leads to urinary excretion, termed "ketonuria." Marked ketonemia and ketonuria are most frequently associated with uncontrolled type 1 diabetes mellitus. In this setting, absolute insulin deficiency limits glucose uptake, promotes unregulated lipolysis, and accelerates ketogenesis. The resulting overproduction of acidic ketone bodies can exceed the buffering capacity of blood, causing metabolic acidosis. This condition, known as diabetic ketoacidosis (DKA), constitutes a serious and potentially life-threatening complication requiring prompt treatment. Mastery of the ketogenesis pathway enables clinicians to link biochemical findings with clinical presentations. This integrative approach enhances decision-making in metabolic, endocrine, and nutritional disorders.
β‑hydroxybutyric acid as a potential therapeutic metabolite for type 2 diabetes mellitus (Review).
Type 2 diabetes mellitus (T2DM) is a major metabolic disease that poses a threat to human health; therefore, the development of new pharmaceutical therapies for the treatment of T2DM is of great importance. β‑hydroxybutyric acid (β‑HB) is the primary ketone body present in the human body. β‑HB not only serves as an energy substrate to maintain the metabolic homeostasis of the body but also acts as a signaling molecule, exerting multiple biological functions both inside and outside cells. The present review summarizes the research progress and latest findings of β‑HB in T2DM models from the perspective of metabolism, physiological effects and potential as a therapeutic agent. Research indicates that β‑HB exerts protective effects against T2DM by regulating glucose and lipid metabolism, preserving the integrity of pancreatic β‑cells and improving insulin resistance (IR). Additionally, β‑HB can alleviate the core pathological conditions of T2DM and related complications by enhancing the stability of cellular proteins, reducing oxidative stress and controlling inflammatory responses and endoplasmic reticulum stress (ERS), while regulating mitochondrial biogenesis, autophagy and apoptosis. Furthermore, the present review also describes the application of β‑HB in clinical research on T2DM. Research indicates that regulating β‑HB levels through endogenous and exogenous ketogenesis approaches can influence body weight, fasting blood glucose levels, IR and memory ability in T2DM patients. These results suggest that β‑HB is a potential metabolite for T2DM treatment.
Hepatic Ketogenesis Regulates Lipid Homeostasis via ACSL1-mediated Fatty Acid Partitioning.
Liver-derived ketone bodies play an essential role in energy homeostasis during fasting by supplying fuel to the brain and peripheral tissues. Ketogenesis also helps to remove excess acetyl-CoA generated from fatty acid oxidation, thereby protecting against diet-induced hepatic steatosis. Despite this, the role of ketogenesis in fasting-associated hepatocellular lipid metabolism has not been thoroughly investigated. We used mice with liver-specific knockout of HMGCS2 mice to determine how ACSL1-mediated esterification contributes to fasting-induced steatosis and performed biochemical assays, gene expression profiling, Western blotting, and histologic analyses. We further investigated the association between HMGCS2 expression, lipid re-esterification, and steatosis using human primary hepatocytes and liver samples from patients with metabolic dysfunction-associated steatohepatitis. We show that ketogenic insufficiency, achieved through disrupting hepatic HMGCS2, worsens liver steatosis in both fasted chow-fed and high-fat-fed mice. Our findings indicate that hepatic steatosis arises from increased fatty acid partitioning to the endoplasmic reticulum (ER) for re-esterification, a process mediated by acyl-CoA synthetase long-chain family member 1 (ACSL1). Mechanistically, the accumulation of acetyl-CoA because of impaired hepatic ketogenesis drives the elevated translocation of ACSL1 to the ER. Furthermore, our study reveals heightened ER-localized ACSL1 and lipid re-esterification in human metabolic dysfunction-associated steatohepatitis cases exhibiting impaired hepatic ketogenesis. We also demonstrate that L-carnitine, which buffers excess acetyl-CoA, reduces ER-associated ACSL1 and alleviates hepatic steatosis. Hepatic ketogenesis plays a crucial role in maintaining intracellular acetyl-CoA balance, regulating lipid partitioning, and preventing the development of fasting-induced hepatic steatosis.
The Multifaceted Influence of Beta-Hydroxybutyrate on Autophagy, Mitochondrial Metabolism, and Epigenetic Regulation.
Beta-hydroxybutyrate (BHB), a key ketone body produced during fatty acid metabolism, plays critical roles in various physiological and pathological conditions. Synthesized in the liver through ketogenesis, BHB serves as an essential energy substrate during glucose deprivation, supporting survival by efficiently utilizing fat reserves. It crosses the blood-brain barrier, providing energy for neuronal function, enhancing cognitive processes such as learning and memory, and offering neuroprotection by modulating synaptic plasticity and neurotransmitter levels. BHB's impact extends to cellular pathways, including autophagy, mitochondrial biogenesis, and epigenetic regulation. By modulating autophagy, BHB ensures mitochondrial integrity and function through intricate molecular pathways involving AMPK, mTOR, PINK1/Parkin, and others. This regulation plays vital roles in neurodegenerative diseases, metabolic disorders, cancer, and cardiovascular diseases, reducing oxidative stress and preventing cellular dysfunction. Epigenetically, BHB acts as an endogenous histone deacetylase inhibitor, inducing beneficial histone modifications that enhance cellular resilience and stress responses. This epigenetic influence is crucial in conditions like diabetes and cancer, aiding insulin secretion, protecting pancreatic beta cells, and impacting cancer cell gene expression and survival. Furthermore, BHB's therapeutic potential is evident in its ability to improve mitochondrial function across various tissues, including neurons, muscle, and liver. By enhancing mitochondrial respiration, reducing oxidative stress, and altering metabolic pathways, BHB mitigates conditions such as ICU-acquired weakness, nonalcoholic fatty liver disease, and cardiovascular diseases. BHB's modulation of autophagy and epigenetic regulation underscores its comprehensive role in cellular homeostasis and health across multiple physiological contexts, providing a foundation for future therapeutic strategies.
📚 EuropePMCmostrando 117
Distinct effects of ketogenic and non-ketogenic weight-loss diets on hepatic steatosis and mitochondrial metabolism in MASLD.
Journal of hepatologyRenal Ketogenesis Protects Against Ischemic Kidney Injury.
Journal of the American Society of Nephrology : JASNβ‑hydroxybutyric acid as a potential therapeutic metabolite for type 2 diabetes mellitus (Review).
International journal of molecular medicineMinimum Dietary Fat Threshold for Effective Ketogenesis and Obesity Control in Mice.
NutrientsPerioperative Anesthetic Considerations in HMG-CoA Lyase Deficiency: Case Report and Literature Review.
Journal of clinical medicineBreaking the metabolic-inflammatory vicious cycle in polycystic ovary syndrome: a comparative review of ketogenic and high-fat diets.
Lipids in health and diseaseMechanisms of SIRT3 Regulation of Aging and Aging-Related Diseases and Advances in Drug Therapy.
GerontologyHepatic Ketogenesis Regulates Lipid Homeostasis via ACSL1-mediated Fatty Acid Partitioning.
Cellular and molecular gastroenterology and hepatologyGlial adaptations to high-fat diet in the mediobasal hypothalamus and effects on metabolic control.
Physiology & behaviorThe Multifaceted Influence of Beta-Hydroxybutyrate on Autophagy, Mitochondrial Metabolism, and Epigenetic Regulation.
Journal of cellular biochemistryLiver Metabolism at the Crossroads: The Reciprocal Control of Nutrient-Sensing Nuclear Receptors and Autophagy.
International journal of molecular sciencesDietary lipids, not ketone body metabolites, influence intestinal tumorigenesis in a ketogenic diet.
bioRxiv : the preprint server for biologySustained Glucose Turnover Flux Distinguishes Cancer Cachexia from Nutrient Limitation.
bioRxiv : the preprint server for biologyInduction of Fructose Mediated De Novo Lipogenesis Coexists with the Upregulation of Mitochondrial Oxidative Function in Mice Livers.
The Journal of nutritionFatty acid metabolism: The crossroads in intestinal homeostasis and tumor.
Metabolism: clinical and experimentalKetogenesis mitigates metabolic dysfunction-associated steatotic liver disease through mechanisms that extend beyond fat oxidation.
The Journal of clinical investigationThe Heart Has Intrinsic Ketogenic Capacity that Mediates NAD+ Therapy in HFpEF.
Circulation researchThe Influence of Physical Exercise, Ketogenic Diet, and Time-Restricted Eating on De Novo Lipogenesis: A Narrative Review.
NutrientsImpact of Dapagliflozin on Hepatic Lipid Metabolism and a Dynamic Model of Ketone Body Levels.
The AAPS journalIdentification of chikusetsusaponin IVa as a novel lysine-specific demethylase 1 inhibitor that ameliorates high fat diet-induced MASLD in mice.
Acta pharmacologica SinicaBranched-chain amino acids alleviate NAFLD via inhibiting de novo lipogenesis and activating fatty acid β-oxidation in laying hens.
Redox biologyAdipocyte metabolic state regulates glial phagocytic function.
bioRxiv : the preprint server for biologyEthnic differences in postprandial fatty acid trafficking and utilization between overweight and obese White European and Black African-Caribbean men.
American journal of physiology. Endocrinology and metabolismMetabolic aspects of glycogenolysis with special attention to McArdle disease.
Molecular genetics and metabolismThe interplay between glucose and ketone bodies in neural stem cell metabolism.
Journal of neuroscience researchRestoration of HMGCS2-mediated ketogenesis alleviates tacrolimus-induced hepatic lipid metabolism disorder.
Acta pharmacologica SinicaAdaptive Metabolic Responses Facilitate Blood-Brain Barrier Repair in Ischemic Stroke via BHB-Mediated Epigenetic Modification of ZO-1 Expression.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)Hepatic signal transducer and activator of transcription-3 signalling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis.
Journal of cachexia, sarcopenia and muscleRelationship between serum β-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD.
American journal of physiology. Endocrinology and metabolism[Ketone Body Metabolism and Renal Diseases].
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science editionKetone bodies mediate alterations in brain energy metabolism and biomarkers of Alzheimer's disease.
Frontiers in neuroscienceDietary pattern and hepatic lipid metabolism.
Liver research (Beijing, China)Changes in Plasma Pyruvate and TCA Cycle Metabolites upon Increased Hepatic Fatty Acid Oxidation and Ketogenesis in Male Wistar Rats.
International journal of molecular sciencesFrom common to rare: repurposing of bempedoic acid for the treatment of glycogen storage disease type 1.
Genes & nutritionIdentification of 3H-benzo[b] [1,4] diazepine derivatives as PPARα agonists by in silico studies and biochemical evaluation.
Journal of biomolecular structure & dynamicsDietary Regulation of Hepatic Triacylglycerol Content-the Role of Eucaloric Carbohydrate Restriction with Fat or Protein Replacement.
Advances in nutrition (Bethesda, Md.)Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish.
International journal of molecular sciencesPAQR9 regulates glucose homeostasis in diabetic mice and modulates insulin secretion in β cells in vitro under stress conditions.
Molecular and cellular endocrinologyMLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies.
Metabolism: clinical and experimentalPersistent fasting lipogenesis links impaired ketogenesis with citrate synthesis in humans with nonalcoholic fatty liver.
The Journal of clinical investigationA Young Female With Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD): A Case Report.
CureusRenal and Cardiovascular Metabolic Impact Caused by Ketogenesis of the SGLT2 Inhibitors.
International journal of molecular sciencesThe metabolomics of a protein kinase C delta (PKCδ) knock-out mouse model.
Metabolomics : Official journal of the Metabolomic SocietyCircadian clock controls rhythms in ketogenesis by interfering with PPARα transcriptional network.
Proceedings of the National Academy of Sciences of the United States of AmericaIntegrating the contributions of mitochondrial oxidative metabolism to lipotoxicity and inflammation in NAFLD pathogenesis.
Biochimica et biophysica acta. Molecular and cell biology of lipidsCoA in Health and Disease.
International journal of molecular sciencesMitochondrial Dysfunction and Acute Fatty Liver of Pregnancy.
International journal of molecular sciencesSchisandrin B mitigates hepatic steatosis and promotes fatty acid oxidation by inducing autophagy through AMPK/mTOR signaling pathway.
Metabolism: clinical and experimentalKetogenesis acts as an endogenous protective programme to restrain inflammatory macrophage activation during acute pancreatitis.
EBioMedicineThe Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation.
International journal of molecular sciencesWhat are the clues for an inherited metabolic disorder in Reye syndrome? A single Centre study of 58 children.
Molecular genetics and metabolismBasal Autophagy Is Necessary for A Pharmacologic PPARα Transactivation.
CellsDetecting de novo Hepatic Ketogenesis Using Hyperpolarized [2-13C] Pyruvate.
Frontiers in physiologyMetabolites and Genes behind Cardiac Metabolic Remodeling in Mice with Type 1 Diabetes Mellitus.
International journal of molecular sciencesBlueberry Counteracts Prediabetes in a Hypercaloric Diet-Induced Rat Model and Rescues Hepatic Mitochondrial Bioenergetics.
NutrientsThree Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency.
Frontiers in pediatricsMulti-omics of a pre-clinical model of diabetic cardiomyopathy reveals increased fatty acid supply impacts mitochondrial metabolic selectivity.
Journal of molecular and cellular cardiologyStatus epilepticus and coma leading to death in a boy caused by Medium-chainacyl-coA dehydrogenase deficiency.
Iranian journal of child neurologyHepatocyte-specific fibroblast growth factor 21 overexpression ameliorates high-fat diet-induced obesity and liver steatosis in mice.
Laboratory investigation; a journal of technical methods and pathologyMetabolism as Disease Tolerance: Implications for Sepsis-Associated Acute Kidney Injury.
NephronGallic Acid Ameliorated Impaired Lipid Homeostasis in a Mouse Model of High-Fat Diet-and Streptozotocin-Induced NAFLD and Diabetes through Improvement of β-oxidation and Ketogenesis.
Frontiers in pharmacologyPlasma 3-hydroxyisobutyrate (3-HIB) and methylmalonic acid (MMA) are markers of hepatic mitochondrial fatty acid oxidation in male Wistar rats.
Biochimica et biophysica acta. Molecular and cell biology of lipidsChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue.
Frontiers in endocrinologyProteome and phosphoproteome characterization of liver in the postprandial state from diet-induced obese and lean mice.
Journal of proteomicsCR reprograms acetyl-CoA metabolism and induces long-chain acyl-CoA dehydrogenase and CrAT expression.
Aging cellContributions of Fat and Carbohydrate Metabolism to Glucose Homeostasis in Childhood Change With Age and Puberty: A 12-Years Cohort Study (EARLYBIRD 77).
Frontiers in nutritionMetabolic alterations in dairy cows with subclinical ketosis after treatment with carboxymethyl chitosan-loaded, reduced glutathione nanoparticles.
Journal of veterinary internal medicineBranched chain amino acids and carbohydrate restriction exacerbate ketogenesis and hepatic mitochondrial oxidative dysfunction during NAFLD.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyRole of ketogenic starvation sensors in mediating the renal protective effects of SGLT2 inhibitors in type 2 diabetes.
Journal of diabetes and its complicationsADSA Foundation Scholar Award: Influencing hepatic metabolism: Can nutrient partitioning be modulated to optimize metabolic health in the transition dairy cow?
Journal of dairy scienceEffect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease.
Proceedings of the National Academy of Sciences of the United States of AmericaRole of Deranged Energy Deprivation Signaling in the Pathogenesis of Cardiac and Renal Disease in States of Perceived Nutrient Overabundance.
CirculationHepatic Mitochondrial Oxidative Metabolism and Lipogenesis Synergistically Adapt to Mediate Healthy Embryonic-to-Neonatal Transition in Chicken.
Scientific reportsLiver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile.
Molecular therapy. Nucleic acidsPPARA/RXRA signalling regulates the fate of hepatic non-esterified fatty acids in a sheep model of maternal undernutrition.
Biochimica et biophysica acta. Molecular and cell biology of lipidsKetogenic Diet: A New Light Shining on Old but Gold Biochemistry.
NutrientsMitochondrial dysfunction, AMPK activation and peroxisomal metabolism: A coherent scenario for non-canonical 3-methylglutaconic acidurias.
BiochimieExogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models.
NutrientsAdipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones.
Critical care (London, England)Multi-omics insights into functional alterations of the liver in insulin-deficient diabetes mellitus.
Molecular metabolismLinking bioenergetic function of mitochondria to tissue-specific molecular fingerprints.
American journal of physiology. Endocrinology and metabolismMaternal undernutrition induces fetal hepatic lipid metabolism disorder and affects the development of fetal liver in a sheep model.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyImpaired ketogenesis and increased acetyl-CoA oxidation promote hyperglycemia in human fatty liver.
JCI insightRole of ketone signaling in the hepatic response to fasting.
American journal of physiology. Gastrointestinal and liver physiologyKetogenic and anaplerotic dietary modifications ameliorate seizure activity in Drosophila models of mitochondrial encephalomyopathy and glycolytic enzymopathy.
Molecular genetics and metabolismMetabolic effects of glucagon in humans.
Journal of clinical & translational endocrinologyPersistent Hypoglycemia in Children: Targeted Gene Panel Improves the Diagnosis of Hypoglycemia Due to Inborn Errors of Metabolism.
The Journal of pediatricsOral nitrite restores age-dependent phenotypes in eNOS-null mice.
JCI insightTissue acylcarnitine status in a mouse model of mitochondrial β-oxidation deficiency during metabolic decompensation due to influenza virus infection.
Molecular genetics and metabolismEmulsification Increases the Acute Ketogenic Effect and Bioavailability of Medium-Chain Triglycerides in Humans: Protein, Carbohydrate, and Fat Metabolism.
Current developments in nutritionHepatic ketogenic insufficiency reprograms hepatic glycogen metabolism and the lipidome.
JCI insightAcetylcholinesterase Inhibitor Donepezil Effects on Plasma β-Hydroxybutyrate Levels in the Treatment of Alzheimer's Disease.
Current Alzheimer researchAcetyl-CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents.
Hepatology (Baltimore, Md.)Dendritic peptide bolaamphiphiles for siRNA delivery to primary adipocytes.
BiomaterialsDEPP/DEPP1/C10ORF10 regulates hepatic glucose and fat metabolism partly via ROS-induced FGF21.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyExercise decreases CLK2 in the liver of obese mice and prevents hepatic fat accumulation.
Journal of cellular biochemistryMitochondrial 3-Hydroxy-3-Methylglutaryl-CoA Synthase Deficiency: Unique Presenting Laboratory Values and a Review of Biochemical and Clinical Features.
JIMD reportsNrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders.
Molecular metabolismHigh non-esterified fatty acid concentrations promote expression and secretion of fibroblast growth factor 21 in calf hepatocytes cultured in vitro.
Journal of animal physiology and animal nutritionHepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones.
The Journal of endocrinologyThe desert gerbil Psammomys obesus as a model for metformin-sensitive nutritional type 2 diabetes to protect hepatocellular metabolic damage: Impact of mitochondrial redox state.
PloS oneDiagnosis of LCHAD/TFP deficiency in an at risk newborn using umbilical cord blood acylcarnitine analysis.
Molecular genetics and metabolism reportsMedium-chain acyl-Coenzyme A dehydrogenase deficiency (MCADD): a cause of severe hypoglycaemia in an apparently well child.
BMJ case reportsTanycytes and a differential fatty acid metabolism in the hypothalamus.
GliaMetabolomic Profile of Low-Copy Number Carriers at the Salivary α-Amylase Gene Suggests a Metabolic Shift Toward Lipid-Based Energy Production.
DiabetesInhibition of Pyruvate Dehydrogenase Kinase 2 Protects Against Hepatic Steatosis Through Modulation of Tricarboxylic Acid Cycle Anaplerosis and Ketogenesis.
DiabetesMedium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects.
Neurobiology of agingMeasuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-(13)C]butyrate and [1-(13)C]pyruvate.
Scientific reportsHyperketonemia and ketosis increase the risk of complications in type 1 diabetes.
Free radical biology & medicineFatty acids and their therapeutic potential in neurological disorders.
Neurochemistry internationalLipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity.
American journal of physiology. Endocrinology and metabolismLongitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy.
PloS oneExercise and the Regulation of Hepatic Metabolism.
Progress in molecular biology and translational sciencePCB126-Induced Disruption in Gluconeogenesis and Fatty Acid Oxidation Precedes Fatty Liver in Male Rats.
Toxicological sciences : an official journal of the Society of ToxicologyRole of the Wnt/β-Catenin Pathway in the Pathogenesis of Alcoholic Liver Disease.
Current molecular pharmacologyKetone Body Therapy Protects From Lipotoxicity and Acute Liver Failure Upon Pparα Deficiency.
Molecular endocrinology (Baltimore, Md.)Phosphorylation of the nuclear receptor corepressor 1 by protein kinase B switches its corepressor targets in the liver in mice.
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Distinct effects of ketogenic and non-ketogenic weight-loss diets on hepatic steatosis and mitochondrial metabolism in MASLD.
- Renal Ketogenesis Protects Against Ischemic Kidney Injury.
- β‑hydroxybutyric acid as a potential therapeutic metabolite for type 2 diabetes mellitus (Review).
- Hepatic Ketogenesis Regulates Lipid Homeostasis via ACSL1-mediated Fatty Acid Partitioning.
- The Multifaceted Influence of Beta-Hydroxybutyrate on Autophagy, Mitochondrial Metabolism, and Epigenetic Regulation.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:309115(Orphanet)
- MONDO:0017713(MONDO)
- GARD:21317(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Q55787301(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar