Glucose glycolytic degradation

How is it possible that both the glycolytic degradation of glucose to lactate and the reverse process, formation of glucose from lactate (gluconeogenesis), are energetically favorable ... 

The glycolytic pathway by which glucose is degraded to pyruvate. 

Gluconeogenesis from pyruvate is not equal to the reverse process of glycolytic degradation of glucose to this 3-carbon intermediate. The glycolytic pathway and the gluconeogenetic pathway deviate at three steps. The conversion of pyruvate to PEP is not mediated by pyruvate kinase due to the irreversible nature of this metabolic step. Pyruvate, derived from either lactate or alanine, is converted to oxaloacetate in the mitochondrial matrix. This step is catalyzed by pyruvate carboxylase. Oxaloacetate per se cannot pass the mitochondrial inner membrane. However, with the use of the malate-aspartate shuttle, the 4-carbon skeleton of oxaloacetate can be transferred into the cytoplasmic compartment. Then oxaloacetate is converted to PEP by the action of PEP carboxykinase (Figure 1). 

The rate of the gluconeogenetic pathway is regulated primarily by the enzymes that bypass the irreversible steps in glycolytic degradation of glucose to pyruvate. 

List the alternative end points of the glycolytic degradation of glucose. 

Figure 6 Fatty-acid biosynthesis. Cytoplasmic acetyl-CoA (AcCoA) is the primary substrate for de novo fatty-acid synthesis. This two-carbon compound most commonly derives from the glycolytic degradation of glucose, and its formation is dependent upon several reactions in the mitochondria. The mitochondrial enzyme pyruvate carboxylase is found primarily in tissues that can synthesize fatty acids. AcCoA is converted to maionyl-CoA (MalCoA) by acetyl-CoA carboxylase. Using AcCoA as a primer, the fatty-acid synthase multienzyme complex carries out a series of reactions that elongate the growing fatty acid by two carbon atoms. In this process MalCoA condenses with AcCoA, yielding an enzyme-bound four-carbon /3-ketoacid that is reduced, dehydrated, and reduced again. The product is enzyme-bound 4 0. This process is repeated six more times, after which 16 0 is released from the complex. The reductive steps require NADPH, which is derived from enzyme reactions and pathways shown in grey. Enz refers to the fatty acid synthase multienzyme complex.

By combining the glycolytic pathway, the Krebs cycle, and oxidative phosphorylation, the energy yield from the aerobic degradation of glucose will be... 

Scheme 9.4 Biochemical retrosynthesis of 2 -deoxyribo-nucleosides from glucose, acetaldehyde and a nucleobase (adenine) through the glycolytic pathway and the reverse reactions of 2 -deoxyribonucleoside degradation.

Scheme 9.5 Multi-step enzymatic process for 2 -deoxyribo-nucleoside production from glucose, acetaldehyde and a nucleobase through glycolysis, reverse reactions of 2 -deoxy-ribonucleoside degradation and ATP regeneration by the yeast glycolytic pathway recycling the phosphate generated by nucleoside phosphorylase.

The oxidative pentose phosphate cycle is often presented as a means for complete oxidation of hexoses to C02. For this to happen the C3 unit indicated as the product in Fig. 17-8A must be converted (through the action of aldolase, a phosphatase, and hexose phosphate isomerase) back to one-half of a molecule of glucose-6-P which can enter the cycle at the beginning. On the other hand, alternative ways of degrading the C3 product glyceraldehyde-P are available. For example, using glycolytic enzymes, it can be oxidized to pyruvate and to C02 via the citric acid cycle. 

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. 

The cycle oxidizes pyruvate (formed during the glycolytic breakdown of glucose) to C02 and H20, with the concomitant production of energy. Acetyl CoA from fatty acid breakdown and amino acid degradation products are also oxidized. In addition, the cycle has a role in producing precursors for biosynthetic pathways. 

The citric acid cycle, also known as the TCA (tricarboxylic acid) cycle or Krebs cycle (after its discoverer in 1937), is used to oxidize the pyruvate formed during the glycolytic breakdown of glucose into C02 and H20. It also oxidizes acetyl CoA arising from fatty acid degradation (Topic K2), and amino acid degradation products (Topic M2). In addition, the cycle provides precursors for many biosynthetic pathways. 

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