Pyruvate glycolytic pathway

Determine the anticipated location in pyruvate of labeled carbons if glucose molecules labeled (in separate experiments) with " C at each position of the carbon skeleton proceed through the glycolytic pathway. 

Deficiency of pyruvate kinase (PK) is the most common and well-characterized enzymatic deficiency involving the glycolytic pathway and causing hereditary he-... 

Figure 6.5 Details of the glycolytic pathway. All the enzymes except pyruvate dehydrogenase are present in the cytosol. The pathway, presently the molecular structured of the intermediates, is described in Appendix 6.3.

Enols and enolization feature prominently in some of the basic biochemical pathways (see Chapter 15). Biochemists will be familiar with the terminology enol as part of the name phosphoenolpyruvate, a metabolite of the glycolytic pathway. We shall here consider it in non-ionized form, i.e. phosphoenolpyruvic acid. As we have already noted (see Section 10.1), in the enolization between pyruvic acid and enolpyruvic acid, the equilibrium is likely to favour the keto form pyruvic acid very much. However, in phosphoenolpyruvic acid the enol hydroxyl is esterified with phosphoric acid (see Section 7.13.2), effectively freezing the enol form and preventing tautomerism back to the keto form. 

The glycolytic pathway, or glycolysis, is a metabolic sequence in which glucose is broken down to pyruvic acid. The subsequent fate of pyruvate then depends upon whether or not the organism is aerobic or anaerobic Under aerobic conditions, pyruvate is oxidized via oxidative phosphorylation under anaerobic conditions, pyruvate is converted further into compounds such as lactate or ethanol, depending upon the organism. 

We have just seen that anaerobic organisms metabolize pyruvate from the glycolytic pathway by various means, but that the prime objective is to reoxidize NADH to NAD+. In aerobic organisms, reoxidation of NADH is achieved via oxidative phosphorylation, generating ATP in the process, and... 

The requirement for NAD+ is to reoxidize the lipoic acid carrier. It is worth mentioning that the pyruvate acetaldehyde conversion we considered at the end of the glycolytic pathway involves the same initial sequence, and pyruvate decarboxylase is another thiamine diphosphate-dependent enzyme. 

In the overall glycolytic process, one molecule of glucose is converted to two molecules of pyruvate (the pathway of carbon). Two molecules of ADP and two of Pi are converted to two molecules of ATP (the pathway of phosphoryl groups). Four electrons, as two hydride ions, are transferred from two molecules of glyceralde-hyde 3-phosphate to two of NAD+ (the pathway of electrons). 

The glycolytic pathway produces pyruvate, which is the primary source of the mitochondrial acetyl CoA to be used for fatty acid synthesis. It also produces cytosolic reducing equivalents of NADH. Pyruvate enters the mitochondria. 

Glycolysis, the anaerobic degradation of glucose to pyruvate, generates ATP (equation 10.16). The glycolytic pathway is regulated to meet the cellular requirements for this important energy source. 

Glucose is converted to pyruvate by the glycolytic pathway (Fig. 5.20). Pyruvate is then oxidised to acetyl-CoA and C02 by the pyruvate decarboxylase enzyme ... 

The glycolytic pathway from glucose to pyruvate, indicating two anaerobic options (ethanol or lactate) and one aerobic option (TCA cycle). The red arrow indicates how NADH formed in glycolysis... 

The final energy payoff in the glycolytic pathway occurs in the hydrolysis of phosphoenolpyruvate to pyruvate and the concomitant phosphorylation of ADP to ATP. Two molecules of ATP are produced for each molecule of hexose phosphate consumed, bringing the net yield of ATP to two molecules for each molecule of glucose (two molecules of ATP are regenerated in the phosphoglycerate kinase step and two in this step, and two are consumed in the hexoki-nase and phosphofructokinase steps). 

Under aerobic conditions, the glycolytic pathway becomes the initial phase of glucose catabolism (fig. 13.2). The other three components of respiratory metabolism are the tricarboxylic acid (TCA) cycle, which is responsible for further oxidation of pyruvate, the electron-transport chain, which is required for the reoxidation of coenzyme molecules at the expense of molecular oxygen, and the oxidative phosphorylation of ADP to ATP, which is driven by a proton gradient generated in the process of electron transport. Overall, this leads to the potential formation of approximately 30 molecules of ATP per molecule of glucose in the typical eukaryotic cell. 

Deoxy-D-xylulose 5-phosphate is formed from the glycolytic pathway intermediates pyruvic acid and glyceraldehyde 3-phosphate with the loss of the pyruvate carboxyl (Figure 5.6). Thiamine diphosphate-mediated decarboxylation of pyruvate... 

---