The Citric Acid Cycle
To recap: Living organisms demand a constant supply of energy for a variety of reasons but ultimately for survival. Systems have compiled in an organised and complex structure to meet those demands. The citric acid cycle holds major importance in the energy-yielding metabolic pathway that is vital for organisms to survive. Not only does the cycle provide the coenzymes that contribute to adenosine triphosphate production, but also is essential for synthesising a variety of carbon compounds. The cycle is a dominant stage in the energy-producing catabolic pathway that is conserved in all kingdoms of life. Errors in the cycle constitute a collection of unique human diseases with symptoms ranging from developmental delay, severe mental retardation, language impairment, seizures and dysmorphic facial features.
Changes in the levels of calcium regulates the citric acid cycle. Calcium accumulation can activate pyruvate dehydrogenase phosphatase which then activates the pyruvate dehydrogenase complex. During exercise, ADP and pyruvate concentrations will rise as muscle contraction uses ATP, and glucose is converted into pyruvate to fulfil respiratory demands. ADP and pyruvate activate dehydrogenase by inhibition of kinases. Calcium levels rise through muscle contraction and so phosphatases are stimulated, enhancing dehydrogenase activity. This in turn means that more acetyl-CoA can be produced to enter the citric acid cycle for respiration or to produce carbon skeletons.
Phophatase defeiciency results in dehydrogenase being inactive due to being phosphorylated. This means that rather than glucose being converted into acetyl-CoA, it becomes lactic acid. Lactic acid buildup causes issues for tissue functioning and the central nervous system.
Additionally, calcium activates isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase thus increasing the rate of stages in the citric acid cycle. These allosteric enzymes are the primary control points for the citric acid cycle as they are the first two enzymes to generate high-energy electrons.
Isocitrate needs an enhanced affinity to substrate, this is stimulated by ADP and inhibited by ATP. NADH inhibits isocitrate dehydrogenase by displacing NAD which is needed for later steps in the cycle. Alpha-ketoglutarate dehydrogenase controls the rate of the cycle, and is inhibited by the products of the reactions it catalyses (succinyl CoA and NADH) and high energy change. Deficiency in the enzyme results in numerous neurological disorders. The two enzymes connect the cycle with other pathways, highlighting that the cycle is the significant hub for metabolism.
Conclusively, the citric acid cycle holds a major role in biosynthetic metabolism and functions as a hub to facilitate traffic flow. Glycolysis alone is not sufficient in producing precursors for complete aerobic respiration, and so there is a great reliance on an efficient metabolic system that meets the fuel demands for all organisms. In addition to this important role, its provision for carbon skeleton biosynthesis enhances its dominance. The cycle connects carbohydrate, fat and protein metabolism and without it cellular aerobic respiration would be incomplete. The cycle is a multi-functioning system which we need in order to eat, breath and survive.