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  1. Carbohydrate Metabolism and Respiration in Algae
  2. The evolution of the Krebs cycle: A promising subject for meaningful learning of biochemistry
  3. Citric acid cycle - Wikipedia
  4. Overview of Metabolism and Metabolic Disorders

Changes in enzymatic function within this carbohydrate metabolic pathway can lead to several diseases, such as diabetes and a multitude of glycogen storage diseases. However, the removal of an -OH group on the ribose sugar is necessary to generate the deoxyribose sugar that makes up the nucleotide building blocks of DNA. The purine and pyrimidine products of DNA and RNA breakdown can either be recycled for future nucleic acid synthesis or removed as waste products.

Carbohydrate Metabolism and Respiration in Algae

The cyclical breakdown and synthesis of the various types of nucleic acids is critical for energy storage and generation and is, therefore, essential for cellular homeostasis. Proteins are composed of amino acids linked in series to form polypeptide chains which, upon three-dimensional folding, form the mature protein. Because proteins constitute a significant portion of all cells, they are also a key nutrient that cells use for fuel and other processes. Digestion of proteins begins in the stomach where stomach acid and the enzyme pepsin break down proteins into simpler polypeptides.

Amino acid breakdown can lead to the production of ammonium ions. Below, we discuss the urea cycle and its role in clearing toxic ammonia. It is important to note that proteins are a very useful source of energy during times of starvation. This is because the breakdown of proteins leads to the creation of metabolic intermediates that can feed into the citric acid cycle discussed below.

Actin filaments have been labeled with DY phalloidin red. Nucleotides fall into two major groups: purines and pyrimidines, both of which are composed of a phosphate group and a pentose sugar but differ in the size of their nitrogenous base. Adenine and guanine are purines, while cytidine, uridine, and thymidine are pyrimidines. ATP and GTP are the primary energy carriers of the cell and contain high levels of energy in the bonds between their phosphate groups. The breaking of one of the bonds leads to the release of energy that can drive cellular functions. Phosphate groups can be sequentially removed via phosphatase enzymes from ATP and GTP to generate adenosine and guanosine di- and mono-phosphates i.

Within the pyrimidine synthesis pathway, there are also UTP and CTP nucleotides, which are derived from uridine and cytidine, respectively. Mitochondria are intracellular organelles that play a central role in cellular metabolism and energetics. These dynamic organelles play critical roles for integrating different metabolic inputs, compartmentalizing key metabolic and cell fate pathways, and acting as the efficient engine that converts nutrient inputs into energy currency, mainly ATP.

Generating ATP from nutrient metabolites is seen as the key aspect of mitochondrial function. The conversion of metabolites from the citric acid cycle into ATP is achieved by the transfer of electrons from these intermediates through the respiratory chain subunits on the mitochondrial inner membrane.

As electrons are transferred, protons are pumped into the inner membrane space, which establishes a biochemical gradient. The key respiratory complexes I, III, and IV reside in the inner mitochondrial membrane and are the protein units that pump the protons from the matrix into the inner membrane space using electrochemical energy derived from the transfer of electrons.

Molecular oxygen is the final electron acceptor from complex IV, resulting in its reduction to H 2 O. Importantly, the imbalance of protons between the mitochondrial matrix and inner membrane space creates an electrochemical gradient, which provides the potential energy to drive ATP synthesis from ADP. This efficient energy-generating process, termed "aerobic respiration" since it depends on oxygen, yields the best energy return ATP on the initial nutrient input compared to other generating processes in the cell such as anaerobic respiration, which does not require oxygen and produces smaller amounts of ATP; this occurs mainly from glycolysis and conversion of glucose to lactic acid.

The evolution of the Krebs cycle: A promising subject for meaningful learning of biochemistry

Mitochondrial function and energy generation are especially critical in energy-demanding tissues and cells of the body, such cells in the brain neurons , heart cardiomyocytes , and pancreas beta-islets. Mitochondrial function is critical for all cells, and disease results when mitochondrial function is compromised.

The severity of the resulting disease depends on the metabolic demands of the affected cell type s. The different metabolic disorders that can arise from mitochondrial dysfunction are reviewed in Section 4. Mitochondria are also known to have a unique physiology that works to regulate their function and impact on cellular metabolism. Mitochondria do not exist as single entities in the cell but instead form a dynamic network throughout the cytoplasm.

The life cycle of a mitochondrion within the network is defined by the processes of biogenesis, fusion and fission, motility, and degradation. Biogenesis is the formation of new mitochondria.

Metabolism - Glycolysis

These processes are continuously happening as mitochondria respond to the variable energetic demands of the cell, and as a response to mitochondrial damage, in order to preserve cellular mitochondrial function. Mitochondrial movement or motility allows mitochondria to move to where their particular functions are needed.

Finally, mitophagy is an autophagy-like process specifically affecting mitochondria which allows for degradation of mitochondrial components. Autophagy especially allows for the removal of damaged mitochondria. Defective mitochondrial autophagy, or mitophagy, leads to buildup of dysfunctional mitochondria. Defects in mitophagy have been implicated in the pathogenesis of some diseases, notably Parkinson's disease. Thus, proper regulation and maintenance of mitochondrial function is a critical aspect for the maintenance of metabolic homeostasis.

Below, we discuss the major metabolic pathways used by cells. Each pathway relies on enzymes to catalyze the specific chemical reactions involved in converting an original metabolic substrate into another through multiple intermediate steps that each produce metabolites. Macrophages can be triggered to recognize antigens, such as damaged cells or foreign material, for on-demand destruction. Macrophages are present in most tissues and respond when needed to infections and dying cells.

The recognized material is destroyed via phagocytosis in the macrophage, which gives the cells their name "big eater" in Greek. Macrophages take various forms when present in different locations and can perform additional functions besides phagocytosis. Upon tissue injury or pathogen infection, monocytes in the blood will be recruited to the affected tissue and differentiate to make macrophages.

Depending on the tissue localization, different types of macrophages exist, such as Kupffer cells in the liver, alveolar macrophages in the lung, microglia in the brain, etc. These different types of macrophages all come from monocytes but specialize their function to the resident tissue. Most of the general phagocytosis function is carried out by resident tissue macrophages. Besides phagocytosing dead cells and foreign material, macrophages can also signal to other immune cells via cytokines.

Citric acid cycle - Wikipedia

To a certain extent, macrophages perform the critical function of antigen presentation, accordingly working together with T cells to support adaptive immunity. Additionally, macrophages can secrete cytokines such as IL and play a role in local immune responses, while others secrete high amounts of IL, which mediates their role in tissue repair. Thus the "big eaters" play a variety of roles in the immune system in addition to the main job of phagocytosis. Glycolysis refers to the intracellular breakdown of glucose into pyruvic acid and ATP. Glycolysis takes place in the cytoplasm and utilizes a series of enzymes to split each six-carbon glucose molecule into two three-carbon pyruvate molecules.

Glycolysis does not require oxygen and is, therefore, the predominant catabolic pathway in anaerobic organisms. Glycolysis is also utilized by "otherwise aerobic" organisms when oxygen is limited. The citric acid cycle, also known as the Krebs cycle, is the next step in intracellular glucose metabolism. It takes place in the mitochondria and is initiated by acetyl coenzyme A acetyl CoA , which is an oxidized derivative of the pyruvate produced during glycolysis.

The citric acid cycle requires oxygen and releases carbon dioxide and water as byproducts. For each glucose molecule, two pyruvates are produced via glycolysis; thus, the citric acid cycle goes around twice and produces two carbon dioxide molecules, three NADH, one FADH 2 , and one ATP for each turn. While the citric acid cycle does not itself produce much ATP, the major energy currency of the cell, the NADH and FADH 2 molecules act as electron carriers that shuttle into the electron transport chain for oxidative phosphorylation and high-energy production.

There are five transmembrane enzyme complexes that drive the transfer of electrons from one molecule to another in a series of redox reactions. This is known as the electron transport chain. The transfer of electrons along the electron transport chain releases energy that then drives proton pumps to translocate protons against their concentration gradient from the mitochondrial matrix, across the inner mitochondrial membrane, and into the intermembrane space.

Accumulated protons in the intermembrane space then pass through the final complex in the electron transport chain, ATP synthase, along their concentration gradient into the mitochondrial matrix. The energy released by protons flowing down their concentration gradient through the ATP synthase molecule drives its function as a "molecular motor" that uses the energy to catalyze the addition of a phosphate group to the ADP precursor, creating ATP. One glucose molecule yields 30 to 36 ATP molecules from oxidative phosphorylation.

As discussed above, in cellular respiration the pyruvate produced during glycolysis is shunted into the citric acid cycle and oxidative phosphorylation. However, there is an alternative cytosolic pathway that branches off glycolysis and leads to the formation of the sugars necessary for DNA and RNA production. The pentose phosphate pathway utilizes a molecule that is produced in the first step of glycolysis—glucosephosphate. Glucosephosphate is generated through the addition of a phosphate group to glucose and is used by the pentose phosphate pathway to generate NADPH, five-carbon sugars known as pentoses, and ribose 5-phosphate, which serve as precursor molecules for nucleotide synthesis.

NADPH plays an important functional role in not only the pentose phosphate pathway but in other biosynthetic processes, including fatty acid metabolism and reactive oxygen species ROS control. Glutamine is an important fuel source in rapidly proliferating cells. It is transported into cells via a specific amino acid transporter and converted into glutamate in the mitochondria.

The urea cycle, also called the ornithine cycle, is necessary to prevent toxic buildup of ammonia in the body and occurs mostly in the liver. It is composed of biochemical reactions that produce urea from ammonium ions that are a byproduct of amino acid breakdown. In this cycle, carbon dioxide combines with the ammonia that is produced from the transamination of amino acids during protein metabolism, resulting in the generation of urea and water that are later eliminated as urine by the kidneys.

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The initial steps of the urea cycle take place in the mitochondria, and the later steps proceed in the cytosol. Fatty acids are both a source and storage unit of energy in the cell. In addition, fatty acids play a major role in cellular signaling and, therefore, heavily influence cellular function. Fatty acid synthesis takes place in the cytosol and involves the creation of fatty acids from acetyl-CoA and NADPH in a process that is catalyzed by fatty acid synthases. Acetyl-CoA units that are necessary for fatty acid synthesis are provided by the breakdown of glucose through glycolysis.

Glucose breakdown also generates glycerol, which can combine with three fatty acid subunits to form triglycerides. Generation of phospholipids is also a critical part of fatty acid metabolism, as phospholipids are a major component of biological membranes.

When glycerol combines with only two fatty acids and a phosphate group, this results in the formation of phospholipids. Phospholipids have many functions within the cell, but, most importantly, they form the lipid bilayer that makes up the cell membrane. Aside from being the building blocks of cell and organelle membranes, phospholipids have been used in drug synthesis to increase permeability across the membrane and to improve drug bioavailability.

Fatty acid beta-oxidation is the process by which fatty acids are broken down into their constituent acetyl-CoA subunits in the mitochondria.

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Gluconeogenesis refers to the generation of glucose from sources other than carbohydrates. Similar to glycogenolysis, gluconeogenesis is an adaptive process that occurs primarily in the liver to ensure that blood glucose levels do not drop too low.


Overview of Metabolism and Metabolic Disorders

Gluconeogenesis usually occurs during periods of low nutrient intake, intense exercise, or low-carbohydrate food consumption. One-carbon metabolism refers to a group of folate-dependent metabolic pathways that are essential for the anabolism of several molecules, such as amino acids and nucleotides. In this pathway, folic acid acts as a carrier of one-carbon groups, facilitating the removal and transfer of these groups from donor molecules.

There are three molecules that can be used to move one-carbon groups: tetrahydrofolate, a folate-derivative that acts as cofactor for several enzymes; s-adenosylmethionine, a methyl donor; and vitamin B12, a coenzyme in methylation and carbon rearrangement reactions. Aside from its role in amino acid and nucleotide synthesis, one-carbon metabolism is also important for DNA and histone methylation.

In mitochondria, the by-products of ATP generation via electron transport include reactive oxygen species ROS , which are highly reactive molecules that can cause oxidative damage to organelles and other cellular structures. At low physiologic levels, ROS toxicity can be adequately controlled by intracellular antioxidant systems, including superoxide dismutase SOD , glutathione, and catalase. Basal ROS levels are also now known to play a critical role in physiological cell pathways.

However, pathological ROS levels have been shown to damage proteins, lipids, and DNA, which can lead to defective mitochondrial metabolism and deleterious consequences for cell function and viability. Effectively coping with ROS-induced mitochondrial damage is key to maintaining cell function and viability under different forms of cellular stress.

Different environmental conditions or cellular perturbations can induce oxidative stress. In the metabolic context, oxidative stress can occur when nutrient supply exceeds energy demand. Under aerobic conditions, the pyruvate generated from glucose is oxidatively decarboxylated to form acetyl CoA. In eukaryotes, the reactions of the citric acid cycle take place inside mitochondria, in contrast with those of glycolysis, which take place in the cytosol Figure The double membrane of the mitochondrion is evident in this electron micrograph.

The numerous invaginations of the inner mitochondrial membrane are called cristae. The oxidative decarboxylation of pyruvate and the sequence of reactions more The citric acid cycle is the central metabolic hub of the cell. It is the gateway to the aerobic metabolism of any molecule that can be transformed into an acetyl group or dicarboxylic acid. The cycle is also an important source of precursors, not only for the storage forms of fuels, but also for the building blocks of many other molecules such as amino acids, nucleotide bases, cholesterol, and porphyrin the organic component of heme.

What is the function of the citric acid cycle in transforming fuel molecules into ATP? Recall that fuel molecules are carbon compounds that are capable of being oxidized—of losing electrons Chapter The citric acid cycle includes a series of oxidation-reduction reactions that result in the oxidation of an acetyl group to two molecules of carbon dioxide. The overall pattern of the citric acid cycle is shown in Figure A four- carbon compound oxaloacetate condenses with a two-carbon acetyl unit to yield a six-carbon tricarboxylic acid citrate.

An isomer of citrate is then oxidatively decarboxylated. Oxaloacetate is then regenerated from succinate. Two carbon atoms enter the cycle as an acetyl unit and two carbon atoms leave the cycle in the form of two molecules of carbon dioxide. The function of the citric acid cycle is the harvesting of high-energy electrons from carbon fuels. Note that the citric acid cycle itself neither generates a large amount of ATP nor includes oxygen as a reactant Figure In oxidative phosphorylation Chapter 18 , electrons released in the reoxidation of NADH and FADH 2 flow through a series of membrane proteins referred to as the electron-transport chain to generate a proton gradient across the membrane.

Overview of the Citric Acid Cycle. Cellular Respiration. The citric acid cycle constitutes the first stage in cellular respiration, the removal of high-energy electrons from carbon fuels left. These electrons reduce O 2 to generate a proton gradient middle , which is used to synthesize more Note in Figure The oxaloacetate acts catalytically: it participates in the oxidation of the acetyl group but is itself regenerated.

Thus, one molecule of oxaloacetate is capable of participating in the oxidation of many acetyl molecules. By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Biochemistry. 5th edition.