Metabolic signaling pathway
Cell homeostasis is regulated by the coordinated activities of several key metabolic pathways. These processes include carbohydrate metabolism, lipid metabolism, glutamine metabolism, and nucleotide metabolism, which maintain the energy state of cells and provide the necessary components to ensure proper cellular function. In turn, many of these metabolic pathways are regulated by extracellular signal transduction. For example, insulin acts through its homologous receptors as the primary hormone that controls key energy functions such as glucose and lipid metabolism.
Carbohydrate metabolism
Carbohydrate metabolism includes all biochemical processes responsible for the formation, breakdown, and mutual conversion of carbohydrates (molecules composed of carbon, hydrogen, and oxygen (CHO)) to ensure a continuous supply of energy to living cells.
lGlucose, the main substrate of metabolism, is absorbed into the blood by the small intestine and circulates to all tissues in the body, where uptake is regulated by insulin signaling, thus providing the majority of an individual's daily energy needs.
lGlucose is further broken down into pyruvate through a process called glycolysis, which produces net adenosine triphosphate (ATP), an important source of energy for living cells.
lIt is converted to polysaccharide glycogen primarily through glycogen generation in the liver and skeletal muscle, where it is used as an emergency fuel reserve and subsequently released as free glucose through glycogen decomposition.
Figure.1 IHC staining of α-amylase
Insulin signaling
Insulin is the main hormone that controls critical energy functions, including glucose and lipid metabolism.
lInsulin binds and activates insulin-receptor tyrosine kinases, which initiate downstream signal transduction primarily through the PI3K/AKT and ERK1/2 pathways, followed by phosphorylation and recruitment of substrate junctions, including the IRS protein family.
lMaintains glucose homeostasis by stimulating glucose uptake by fat and muscle cells and reducing glucose synthesis in the liver.
lInsulin production in the pancreas is regulated by blood sugar levels.
Figure.2 Lipid metabolism
Lipid metabolism
Lipid metabolism includes biological processes involved in the synthesis or degradation of lipids, which are a class of organic compounds including fatty acids or their derivatives that are insoluble in water but soluble in organic solvents.
lLipids act as building blocks for key cellular structures such as membranes, play a role in many cellular signaling networks, and are energy-rich sources of fuel used to support cellular function.
lComplex lipids called triglycerides are broken down by enzymes called lipases during digestion in the mouth and small intestine and transported in the blood via lipoproteins.
lFatty acids are both energy sources and energy storage units in cells. Fatty acids are synthesized in the cytoplasm from acetyl-coA and NADPH in A process catalyzed by fatty acid synthase and subsequently metabolized into phospholipids, which are major components of cell membranes and also play a role in cell signal transduction pathways.
Figure.3 Phosphoacetyl-coa carboxylase IHC
Figure.4 Fatty acid synthase (green) and actin (red) IF
Glutamic acid metabolism
The amino acid glutamine is an important metabolic fuel for rapidly proliferating cells.
lGlutamine is the most abundant free amino acid in circulating and intracellular library.
lAct as a substrate to meet the growing demand for ATP, biosynthetic precursors and reducing agents in dividing cells.
lSpecific amino acid transporters allow glutamine to enter the cell, which is then converted into glutamate in the mitochondria, which is a precursor to the TCA cycle intermediate alpha ketoglutaric acid.
lCancer cells often rely on glutamine metabolism to meet their increased energy needs.
Figure.5 Nucleotide metabolism
Nucleotide metabolism
Nucleotide metabolism is a series of biochemical reactions necessary for the synthesis and degradation of the basic building blocks of nucleic acid, DNA and RNA.
lPurines (adenine and guanine) and pyrimidines (cytidine, uridine and thymidine) are the two main groups of nucleotides. All nucleotides are composed of pentose and phosphate groups, but purines and pyrimidines have different nitrogen base sizes.
lNucleotides in the form of nucleosides triphosphate (ATP, GTP, CTP, and UTP) act as stores of chemical energy required for many cellular functions, including amino acid and protein synthesis, cell migration, and division, and this energy is released by removing phosphates.
lCyclic nucleotide cGMP and cAMP act as key second messengers in many cellular signaling cascades that are modified by a class of enzymes called cyclic nucleotide phosphodiesterases.
Figure.6 CNPase (green) and α/β sheathing green protein (Syn205) (red) IF