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Glycolysis, the pathway of enzymatic reactions responsible for the breakdown of glucose into two trioses and further into pyruvate or lactate, was elucidated in 1940. For more than seven decades, it has been taught precisely the way its sequence was proposed by Embden, Meyerhof and Parnas. Accordingly, two outcomes of this pathway were proposed, an aerobic glycolysis, with pyruvate as its final product, and an anaerobic glycolysis, identical to the aerobic one, except for an additional reaction, where pyruvate is reduced to lactate. Several studies in the 1980s have shown that both muscle and brain tissues can oxidize and utilize lactate as an energy substrate, challenging this monocarboxylate’s reputation as a useless end-product of anaerobic glycolysis. These findings were met with great skepticism about the idea that lactate could be playing a role in bioenergetics. In the past quarter of a century monocarboxylate transporters (MCTs) were identified and localized in both cellular and mitochondrial membranes. A lactate receptor has been identified. Direct and indirect evidence now indicate that the enzyme lactate dehydrogenase (LDH) resides not only in the cytosol, as part of the glycolytic pathway machinery, but also in the mitochondrial outer membrane. The mitochondrial form of the enzyme oxidizes lactate to pyruvate and concomitantly produces the reducing agent NADH. These findings have shed light on a major drawback of the originally proposed aerobic version of the glycolytic pathway i.e., its inability to regenerate NAD+, as opposed to anaerobic glycolysis that features the cyclical ability of regenerating NAD+ upon pyruvate reduction to lactate by the cytosolic form of LDH. The malate-aspartate shuttle (MAS), a major redox shuttle in the brain, was proposed as an alternative pathway for NAD+ generation for aerobic glycolysis. Nonetheless, would MAS really be necessary for that function if glycolysis always proceeds to the end-products, lactate and NAD+? An additional dilemma the originally proposed aerobic glycolysis presents has to do with the glycolytic pathway of erythrocytes, which despite its highly aerobic environment, always produces lactate as its end-product. It is time to reexamine the original, dogmatic separation of glycolysis into two distinct pathways and put to test the hypothesis of a unified, singular pathway, the end-product of which is lactate, the real substrate of the mitochondrial TCA cycle.
Carbohydrates are the most abound macromolecules on earth, and they serve different functions within the cell. The purpose of the book is to provide a glimpse into various aspects of carbohydrates by presenting the research of some of the scientists who are engaged in the development of new tools and ideas used to reveal carbohydrate metabolism in health and diseases and as material to mimic the carbohydrate surfaces that take part in molecular recognition, often from very different perspectives. This book covers broad topics in carbohydrate including quality carbohydrates on the prevention and therapy of noncommunicable diseases, lactate, and glycolysis, as biomass in biofuel production, targets for cancer treatment and as biomaterial.
This book deals with a vital topic: metabolism in the cells of the body and various disorders due to its imbalance and/or diseases that disrupt the metabolism of the body. The objective of this book was to collect and compile up-to-date information from reputed researchers in their respective fields to disseminate the latest information about topics that have profound effects on the metabolic processes in the body including insulin resistance, diabetes mellitus, hypothyroidism, metabolic syndrome, glycogen storage disease, and the urea cycle disorder. In total, there are 12 chapters in this book in which the authors have shared their research findings and real-life experiences in managing their patients.
Mitochondria are sometimes called the powerhouses of eukaryotic cells, because mitochondria are the site of ATP synthesis in the cell. ATP is the universal energy currency, it provides the power that runs all other life processes. Humans need oxygen to survive because of ATP synthesis in mitochondria. The sugars from our diet are converted to carbon dioxide in mitochondria in a process that requires oxygen. Just like a fire needs oxygen to burn, our mitochondria need oxygen to make ATP. From textbooks and popular literature one can easily get the impression that all mitochondria require oxygen. But that is not the case. There are many groups of organismsm known that make ATP in mitochondria without the help of oxygen. They have preserved biochemical relicts from the early evolution of eukaryotic cells, which took place during times in Earth history when there was hardly any oxygen avaiable, certainly not enough to breathe. How the anaerobic forms of mitochondria work, in which organisms they occur, and how the eukaryotic anaerobes that possess them fit into the larger picture of rising atmospheric oxygen during Earth history are the topic of this book.
Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
The Pentose Phosphate Pathway aims to explore the pentose phosphate cycle and the practical techniques applied in its investigation. The main focus of the book is the pentose phosphate cycle in animals as well as microorganisms, and does not discuss the one related to photosynthesis. The book covers the formulation of the pathway, its types, and its alternative formulations; the preparation, processes, and analysis of the pathway; and the enzymes involved. Also covered in the book are the intermediates in intact cells and tissues; distribution of enzymes among different tissues and species; the operation, regulation, and overall control of the pathway; and the clinical, nutritional, and metabolic aspects of the pathway. The text is recommended for biologists and biochemists who would like to understand further the pentose phosphate pathway and the processes related to it.
The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.
Recent determination of genome sequences for a wide range of bacteria has made in-depth knowledge of prokaryotic metabolic function essential in order to give biochemical, physiological, and ecological meaning to the genomic information. Clearly describing the important metabolic processes that occur in prokaryotes under different conditions and in different environments, this advanced text provides an overview of the key cellular processes that determine bacterial roles in the environment, biotechnology, and human health. Prokaryotic structure is described as well as the means by which nutrients are transported into cells across membranes. Glucose metabolism through glycolysis and the TCA cycle are discussed, as well as other trophic variations found in prokaryotes, including the use of organic compounds, anaerobic fermentation, anaerobic respiratory processes, and photosynthesis. The regulation of metabolism through control of gene expression and control of the activity of enzymes is also covered, as well as survival mechanisms used under starvation conditions.