Substrate levels

Equation 1-106 predicts that the initial rate will be proportional to the initial enzyme concentration, if the initial substrate concentration is held constant. If the initial enzyme concentration is held constant, then the initial rate will be proportional to the substrate concentration at low substrate concentrations and independent of the substrate concentration at high substrate levels. The maximum reaction rate for a given total enzyme concentration is... 

Lsocitrate Dehydrogenase—The First Oxidadon in die Cycle m-Ketoglutarate Dehydrogenase—A Second Decarboxylation Succinyl-CoA Synthetase—A Substrate-Level Phosphoryladon Succinate Dehydrogenase—An Oxidadon Involving FAD... 

All six carbons of glucose are liberated as CO2, and a total of four molecules of ATP are formed thus far in substrate-level phosphorylations. The 12 reduced coenzymes produced up to this point can eventually produce a maximum of 34 molecules of ATP in the electron transport and oxidative phosphorylation pathways. A stoichiometric relationship for these subsequent processes is 1... 

Whereas ATP made in glycolysis and the TCA cycle is the result of substrate-level phosphorylation, NADH-dependent ATP synthesis is the result of oxidative phosphorylation. Electrons stored in the form of the reduced coenzymes, NADH or [FADHa], are passed through an elaborate and highly orga-... 

Gluconeogenesis Is Regulated by Allosteric and Substrate-Level Control Mechanisms... 

Where es = number of substrate-level phosphorylations per mole of carbon utilised. For oxidative phosphorylation we can write ... 

You will note that the equation used to determine P/O does not take into account ATP synthesis via substrate level phosphorylation, which is a limitation of the P/O estimation. 

Succinyl-CoA is converted to succinate by the enzyme succinate thiokinase (succinyl-CoA synthetase). This is the only example in the citric acid cycle of substrate-level phosphorylation. Tissues in which glu-coneogenesis occurs (the hver and kidney) contain two isoenzymes of succinate thiokinase, one specific for GDP and the other for ADP. The GTP formed is used for the decarboxylation of oxaloacetate to phos-phoenolpymvate in gluconeogenesis and provides a regulatory hnk between citric acid cycle activity and the withdrawal of oxaloacetate for gluconeogenesis. Nongluconeogenic tissues have only the isoenzyme that uses ADP. 

Figure 16-2. The citric acid cycle the major catabolic pathway for acetyl-CoA in aerobic organisms. Acetyl-CoA, the product of carbohydrate, protein, and lipid catabolism, is taken into the cycle, together with HjO, and oxidized to CO2 with the release of reducing equivalents (2H). Subsequent oxidation of 2H in the respiratory chain leads to coupled phosphorylation of ADP to ATP. For one turn of the cycle, 11 are generated via oxidative phosphorylation and one arises at substrate level from the conversion of succinyl-CoA to succinate.

As a result of oxidations catalyzed by the dehydrogenases of the citric acid cycle, three molecules of NADH and one of FADHj are produced for each molecule of acetyl-CoA catabohzed in one mrn of the cycle. These reducing equivalents are transferred to the respiratory chain (Figure 16-2), where reoxidation of each NADH results in formation of 3 ATP and reoxidation of FADHj in formation of 2 ATP. In addition, 1 ATP (or GTP) is formed by substrate-level phosphorylation catalyzed by succinate thiokinase. 

ATP synthase reaction has been calculated as approximately 51.6 kJ. It follows that the total energy captured in ATP per mole of glucose oxidized is 1961 kJ, or approximately 68% of the energy of combustion. Most of the ATP is formed by oxidative phosphorylation resulting from the reoxidation of reduced coenzymes by the respiratory chain. The remainder is formed by substrate-level phosphorylation (Table 17—1). 

Respiratory chain oxidation of 2 NADH Phosphorylation at substrate level Phosphorylation at substrate level... 

Citric acid cycle Succinate thiokinase Phosphorylation at substrate level 2... 

The basic clinical tool used at the present time Is the competitive ligand binding assay for 25-OH-D. Although concentrations are low In the serum of patients with osteomalacia and v . tamln D deficiency rickets, we have recently noted the Interesting paradox that levels can be only 1/2 normal In the face of oyert bone disease (32). This had led us to propose that substrate levels of 25-OH-D3 available to the hydroxylase In kidney which Is responsible for the conversion of 25-OH-D3 to the tissue active metabolite, l,25(OH)2D3, may be rate limiting for this enzyme. 

Section 5.3.2.3) combined with over-expression of IPPI resulted in enhanced astaxanthin accnmnlation to 1.4 mg/g dry cell weight (DCW). Further increases to 45 mg/g DCW were obtained by random mutagenesis of GGPPS, perhaps by altering enzyme response to substrate-level feedback inhibition. 

What would the initial rate be at a substrate level of 2.0 x 10 5 M if the enzyme concentration were doubled At a 2 x 10"3 M substrate level, how long does it take to achieve 80% conversion at the new enzyme level ... 

The principles of stoichiometry may be used to write the reaction rate in terms of the fraction conversion. The desired conversion level is expressed in terms of the initial substrate level. Thus CAo = 24 kg/m3. At any time the instantaneous concentration of substrate can be written as... 

In environments lacking a suitable external electron acceptor - such as dioxygen, sulfate, or ferric iron - respiration is not possible. Here, many organic compounds may be metabolized by fermenting microorganisms. Microbes of this class may create ATP by a direct coupling mechanism, using a process known as substrate level phosphorylation, SLP with an ion translocation mechanism like that employed by respirers, as already described or by a combination of SLP and ion translocation.1... 

At this point, we have reached the stage where we can describe the adatom-substrate system in terms of the ANG Hamiltonian (Muscat and Newns 1978, Grimley 1983). We consider the case of anionic chemisorption ( 1.2.2), where a j-spin electron in the substrate level e, below the Fermi level (FL) eF, hops over into the affinity level (A) of the adatom, whose j-spin electron resides in the lower ionization level (I), as in Fig. 4.1. Thus, the intra-atomic electron Coulomb repulsion energy on the adatom (a) is... 

Fig. 4.1. Anionic chemisorption energy-level diagram showing transfer of j-spin electron from substrate level ek to affinity level A on adatom, while experiencing Coulomb repulsion U from j-spin electron in ionization level I.

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