Murburn precepts for lactic‐acidosis, Cori cycle, and Warburg effect: Interactive dynamics of dehydrogenases, protons, and oxygen

2021 ◽  
Author(s):  
Kelath Murali Manoj ◽  
Vijay Nirusimhan ◽  
Abhinav Parashar ◽  
Jesucastin Edward ◽  
Daniel Andrew Gideon
Keyword(s):  
Lactic Acidosis ◽  
Warburg Effect ◽  
Cori Cycle ◽  
Interactive Dynamics

scholarly journals Refractory Hyperlactatemia and Hypoglycemia in an Adult with Non-Hodgkin’s Lymphoma: A Case Report and Review of the Warburg Effect

2021 ◽  
pp. 1159-1167
Author(s):  
Zainab Al Maqrashi ◽  
Mary Sedarous ◽  
Avinash Pandey ◽  
Catherine Ross ◽  
Ahraaz Wyne
Keyword(s):  
Lactic Acidosis ◽  
Warburg Effect ◽  
Hodgkin’S Lymphoma ◽  
Abdominal Mass ◽  
Hodgkin's Lymphoma ◽  
Type B ◽  
Elderly Male ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Warburg Effect

Lactate is a byproduct of anaerobic glycolysis, and hyperlactatemia is commonly seen in critically ill patients. We report a case of an elderly male presenting with undifferentiated constitutional symptoms, anemia, thrombocytopenia, severe lactic acidosis, refractory hypoglycemia, and a newly detected abdominal mass. A dedicated workup ruled out infectious etiologies and revealed metastatic non-Hodgkin’s lymphoma. This study explores etiologies of type B lactic acidosis in oncology patients, with a focus on Warburg’s effect, and its potential for prognostication.

scholarly journals Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle

2015 ◽  
Vol 112 (37) ◽  
pp. 11642-11647 ◽  
Author(s):  
Tomohiro Suhara ◽  
Takako Hishiki ◽  
Masataka Kasahara ◽  
Noriyo Hayakawa ◽  
Tomoko Oyaizu ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Oxygen Sensor ◽  
Lethal Dose ◽  
Hypoxia Inducible Factor ◽  
Tolerance Test ◽  
Null Mouse ◽  
Mice Model ◽  
Hypoxic Response ◽  
Cori Cycle

Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyperlacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori cycle, a lactate–glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo 13C-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from 13C-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients.

Type B lactic acidosis due to Warburg effect in a child presenting with T cell acute lymphoblastic leukaemia: a milder phenotype

2020 ◽  
Vol 13 (3) ◽  
pp. e233941
Author(s):  
Sanjeev Khera ◽  
Suman Kumar Pramanik ◽  
Suprita Kalra ◽  
Aradhana Dwivedi
Keyword(s):  
T Cell ◽  
Lactic Acidosis ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Warburg Effect ◽  
Aerobic Glycolysis ◽  
Cellular Level ◽  
Haematological Malignancies ◽  
Type B ◽  
Mild Phenotype

Lactic acidosis (LA) is characterised by persistently increased blood lactate >5 mmol/L. Type A LA due to anaerobic glycolysis is frequently seen during management of haematological malignancies. A rare form of LA known as type B LA, which occurs as a result of metabolic dysregulation at cellular level has been described recently. This has been reported to be because of Warburg effect (WE) or aerobic glycolysis, which is seen in cancerous cells as they rely on aerobic glycolysis rather than oxidative phosphorylation for energy generation. Presence of type B LA at initial presentation of haematological malignancies is a poor prognosticating factor and has rarely been reported in children. We present a child with T cell acute lymphoblastic leukaemia with mild phenotype of type B LA due to WE. She responded dramatically to definitive chemotherapy and tolerated intensive phase of chemotherapy without any significant morbidity.

scholarly journals Lactic Acidosis in Prostate Cancer: Consider the Warburg Effect

2017 ◽  
Vol 10 (3) ◽  
pp. 1085-1091 ◽  
Author(s):  
Johannes C. van der Mijn ◽  
Mathijs J. Kuiper ◽  
Carl E.H. Siegert ◽  
Annabeth E. Wassenaar ◽  
Carel J.M. van Noesel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lactic Acidosis ◽  
Warburg Effect ◽  
Blood Gas Analysis ◽  
Tp53 Gene ◽  
Gas Analysis ◽  
Metabolic Reprogramming ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
The Warburg Effect

Lactic acidosis is a commonly observed clinical condition that is associated with a poor prognosis, especially in malignancies. We describe a case of an 81-year-old patient who presented with symptoms of tachypnea and general discomfort. Arterial blood gas analysis showed a high anion gap acidosis with a lactate level of 9.5 mmol/L with respiratory compensation. CT scanning showed no signs of pulmonary embolism or other causes of impaired tissue oxygenation. Despite treatment with sodium bicarbonate, the patient developed an adrenalin-resistant cardiac arrest, most likely caused by the acidosis. Autopsy revealed Gleason score 5 + 5 metastatic prostate cancer as the most probable cause of the lactic acidosis. Next-generation sequencing indicated a nonsense mutation in the TP53 gene (887delA) and an activating mutation in the PIK3CA gene (1634A>G) as candidate molecular drivers. This case demonstrates the prevalence and clinical relevance of metabolic reprogramming, frequently referred to as “the Warburg effect,” in patients with prostate cancer.

Reverse Warburg Effect in a Patient With Aggressive B-Cell Lymphoma: Is Lactic Acidosis a Paraneoplastic Syndrome?

2013 ◽  
Vol 40 (4) ◽  
pp. 403-418 ◽  
Author(s):  
Ubaldo E. Martinez-Outschoorn ◽  
Diana Whitaker-Menezes ◽  
Matias Valsecchi ◽  
Maria P. Martinez-Cantarin ◽  
Alina Dulau-Florea ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
B Cell ◽  
Paraneoplastic Syndrome ◽  
Warburg Effect ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Reverse Warburg Effect ◽  
Aggressive B Cell Lymphoma

scholarly journals Type B lactic acidosis associated with diffuse large B-cell lymphoma and the Warburg effect

2022 ◽  
Vol 50 (1) ◽  
pp. 030006052110677
Author(s):  
Chunhua Wang ◽  
Zanmei Lv ◽  
Yanwei Zhang
Keyword(s):  
Lactic Acidosis ◽  
B Cell ◽  
Warburg Effect ◽  
Cell Lymphoma ◽  
Rare Complication ◽  
B Cell Lymphoma ◽  
Type B ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
The Warburg Effect

Type B lactic acidosis is a rare complication of non-tissue perfusion abnormalities caused by solid tumors or hematologic malignancies. Herein, we present the case of a 42-year-old man with type B lactic acidosis and hypoglycemia who was found to have a diffuse large B-cell lymphoma. The cause of lactic acidosis and/or hypoglycemia is thought to be the Warburg effect, which is when the metabolic rate of a rapidly growing malignant tumor is very high and dominated by glycolysis. Systemic damage from type B lactic acidosis can occur when the increased rate of glycolysis exceeds the normal muscle and liver lactic acid clearance rate. The Warburg effect is a rare but serious condition that needs to be recognized, not only in diffuse large B-cell lymphoma, but also in other malignancies. The prognosis of lactic acidosis in patients with malignant tumors is very poor. Currently, effective chemotherapy seems to be the only hope for survival.

scholarly journals Confirmed Hypoglycemia Without Whipple Triad: A Rare Case of Hyper-Warburgism

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Itivrita Goyal ◽  
Christopher Ogbuah ◽  
Ajay Chaudhuri ◽  
Timothy Quinn ◽  
Rajeev Sharma
Keyword(s):  
Lactic Acidosis ◽  
Chest Wall ◽  
Warburg Effect ◽  
B Cell Lymphoma ◽  
Glucose Consumption ◽  
Fdg Uptake ◽  
Pet Ct ◽  
Wall Mass ◽  
The Brain ◽  
Chest Wall Mass

Abstract Spontaneous hypoglycemia in nondiabetic patients poses a diagnostic challenge. Hypoglycemia in malignancy has several etiologies; an extremely rare mechanism is the Warburg effect causing excess lactate production and avid glucose consumption. We describe the clinical course of a 52-year-old man admitted for chest wall mass and severe but asymptomatic hypoglycemia. Laboratory workup was obtained for insulin vs noninsulin-mediated hypoglycemia, and biopsy of the chest wall mass and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scan were performed. D10 infusion and intravenous/oral steroids started for severe hypoglycemia. Chemotherapy was initiated after biopsy, and blood glucose (BG) and lactate levels followed with clinical response in tumor size and changes in PET/CT. Investigations were significant for venous BG in the 40s (Ademolus Classification of Hypoglycemia grade 2 hypoglycemia), plasma insulin of less than 2 µU/mL (2-20 µU/mL), C-peptide of 0.2 ng/mL (0.8-6.0 ng/mL), insulin-like growth factor 2 (IGF-2) of 113 ng/mL (333-967 ng/mL), serum lactate of 16 mmol/L (0.5-2 mmol/L), and albumin of 2.3 g/dL (3.4-5.4 g/dL). Biopsy showed diffuse large B-cell lymphoma, and PET revealed highly FDG-avid disease in the chest, abdomen, and pelvis, but no FDG uptake was seen in the brain. Hypoglycemia and lactic acidosis improved remarkably after chemotherapy. PET/CT at 4 weeks showed complete metabolic response with reappearance of physiological FDG uptake in the brain. Noninsulin-mediated hypoglycemia was likely due to the combination of profound malnutrition and rapid glucose use by cancer cells. The patient presented with exaggerated Warburg effect (hyper-Warburgism), evident by extreme glucose consumption, severe lactic acidosis, and large tumor burden on PET/CT. Absence of cognitive symptoms was probably due to use of lactate by the brain. Chemotherapy corrected these abnormalities rapidly, and must be instituted in a timely manner.

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