Energy Systems and ATP: Phosphagen, Glycolytic and Oxidative In our earlier post on the Energy Systems series, we discussed Metabolic Energy Basics — availability and storage. Here we focus on the three energy systems — when and how they are utilized towards ATP production. ATP is a molecule that is used as energy within cells.
Catalytic Mechanism The enzyme does not require metal ions for its activity; one of the amino acids in the active site acts as a general base being able to abstract a hydride ion from the hydroxyl group bound to C1 of glucose 6-phosphate.
This causes glucose 6-phosphate, a cyclic hemiacetal with carbon 1 in the aldehyde oxidation state, to be oxidized to a cyclic ester, namely, a lactone.
Because such histidine is conserved in many of the glucose 6-phosphate dehydrogenases sequenced, it is likely that this catalytic mechanism can be generalized to all glucose 6-phosphate dehydrogenases.
In humans, the enzyme exists in two forms: In fact, the binding of the oxidized coenzyme to a specific site close to the dimer interface, but distant from the active site, is required to maintain its dimeric conformation. Under these conditions the oxidative phase is virtually inactive.
Therefore it is possible to state that the fate of glucose 6-phosphate, an intermediate common to both glycolysis and the phosphogluconate pathway, also depends on the current needs for NADPH.
A second mechanism for the regulation of glucose 6-phosphate dehydrogenase activity calls into question the accumulation of acyl-CoAs, intermediates in fatty acid synthesis.
These molecules, by binding to the dimeric form of the enzyme, lead to dissociation into the constitutive monomers, and then to the loss of the catalytic activity. Insulin up-regulates the expression of the genes for glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Therefore, in the well-fed state, the hormone increases carbon flow through the pentose phosphate pathway and then the production of NADPH.
Insulin also promotes the synthesis of fatty acids. However, in the cell this ring-opening reaction, an hydrolysis, is accelerated by the catalytic action of 6-phosphogluconolactonase EC 3.
The reaction is catalyzed by 6-phosphogluconate dehydrogenase EC 1. It consists of an acid-base catalysis proceeding through a three step mechanism in which two strictly conserved residues, a lysine Lysand a glutamate Gluare involved; in humans, Lys and the Glu This leads to the formation of the 3-keto intermediate and a molecule of NADPH that leaves the active site.
In the second step, the decarboxylation step, 3-ketophosphogluconate, that is very susceptible to decarboxylation, is converted to the cis-1,2-enediol of ribulose 5-phosphate, a high energy intermediate.
The result is the formation of ribulose 5-phosphate. An enediol is an organic compound containing two carbon atoms linked by a double bond and an hydroxyl group -OH bound to both carbon atoms.
The enediol can have cis or trans configuration. Therefore, the oxidative phase of the pentose phosphate pathway ends with the production of ribulose 5-phosphate, namely, the substrate for the reactions of the non-oxidative phase.
The overall equation of the oxidative phase is: This phase begins with two reactions: Enzymatic isomerizations and epimerizations play an important role in carbohydrate metabolism.
In isomerization reactions, the interchange of chemical groups occurs between carbon atoms. This reaction is catalyzed by phosphopentose isomerase or ribose 5-phosphate isomerase EC 5. The formation of the cis-1,2-enediol intermediate occurs via a proton-transfer mechanism common to the aldose-ketose isomerizations.
The proposed catalytic mechanism for phosphopentose isomerase from E. Catalytic Mechanism In the first step, the furanose ring of the substrate is opened, opening induced by the interaction with an aspartic acid residue Asp81 that accepts a proton from the hydroxyl group bound to C-1, whereas it is likely that water is the proton donor.
Once the chain is opened, a glutamic acid residue Glu acts as a general base, as a nucleophile, abstracting a proton bound to the C-2, whereas Asp81 donates a proton. As a result, cis-1,2-enediol intermediate is produced. During the synthesis of ribose 5-phosphate from ribulose 5-phosphate phosphopentose isomerase works in reverse.
Xylulose 5-phosphate is a regulatory molecule that inhibits gluconeogenesis and stimulates glycolysis by controlling the levels of fructose 2,6-bisphosphate in the liver. During the reaction an amino acid residue present in the active site of the enzyme acts as a general base, as a nucleophile, and abstracts a proton bound to the C-3, leading to the formation of the cis-2,3-enediol intermediate.
Then, an acidic amino acid residue donates a proton to C-3, but from the opposite side, hence, with an inversion at C-3 to form xylulose 5-phosphate.
Catalytic Mechanism To this point, the hexose monophosphate shunt has generated for each molecule of glucose 6-phosphate metabolized:There are three major energy systems which are responsible for the resynthesis of ATP (Figure 2).
These systems can be categorised as follows: The Phosphagen System, The Glycolytic System, and Mitochondrial Respiration. Energy production is both time and intensity related.
Running at a very high-intensity, as in sprinting, means that an athlete can operate effectively for only a very short period of time whereas running at a low-intensity, as in gentle jogging, means that an athlete can sustain activity for a long period of time.
Muscle disease: Muscle disease, any of the diseases and disorders that affect the human muscle system.
Diseases and disorders that result from direct abnormalities of the muscles are called primary muscle diseases; those that can be traced as symptoms or manifestations of disorders of nerves or other systems . ATP is produced by the coordinated response of all energy systems contributing to different degrees ATP Resynthesis The energy for all physical activity comes from the conversion of high-energy phosphates (ATP) to lower energy phosphates (ADP, AMP, and inorganic phosphate).
This system produces ATP copiously and is the prime energy source during endurance activities When working at 95% effort these energy pathways are time limited and . Aims for lesson Introduce Energy Systems Understand how they are Accelerate Sports Performance It s the most powerful and therefore has the fastest rate of ATP resynthesis But only lasts for seconds which is .