Brain metabolic adaptations

Cells that do not have mitochondria (such as red blood cells) must use glucose for energy since they have no TCA cycle or oxidative phosphorylation. Without a constant glucose supply, these cells would die. The brain relies heavily on glucose metabolism for energy however, the brain can adapt to use alternative energy sources if glucose is not available. 

The formation of ketone bodies is a consequence of prolonged metabolism of fat (Fig. 17-12). Their formation in the liver actually enables liver to metabolize even more fat by freeing up CoA that would otherwise be tied up as acetyl-CoA waiting to get into the TCA cycle. The liver exports the ketone bodies and other tissues, particularly the brain, can adapt to use them. 

Because glucose is the preferred fuel for the brain, an individual who experiences a rapid fall in glucose concentration leading to acute neuroglycopenia will initially feel confusion and may progress to coma and even death. In the event that the person survives 3-4 days, the brain can adapt its metabolism to utilize ketone bodies, metabolically derived from acetyl-CoA (see Figure 6.17), as a source of energy. 

The metabolic adaptations in starvation serve to minimize protein degradation. Large amounts of ketone bodies are formed by the liver from fatty acids and released into the blood within a few days after the onset of starvation. After several weeks of starvation, ketone bodies become the major fuel of the brain. The diminished need for glucose decreases the rate of muscle breakdown, and so the likelihood of survival is enhanced. 

Describe the metabolic changes that occur after one and three days of starvation. Discuss the metabolic adaptations that occur after prolonged starvation note especially the shift in brain fuels and the decreased rate of protein degradation. 

Metabolic regulators of cerebral tissue PtO are complex and involve both vascular and metabolic adaptations. For the brain, the pattern of adaptation includes sequential responses that raise brain PtO (Xu and LaManna, 2006). The initial response is to increase blood flow, followed by an increase in hematocrit and then microvessel density as a result of angiogenesis (vascular adaptations) (Brown et al., 1985 Beck and Krieglstein, 1987 LaManna et al., 1992 LaManna and Harik, 1997 Dunn et al., 2000 LaManna et al., 2004)... 

McIlwain, H. (1971) Types of metabolic adaption in the brain. Essays in Biochemistry, 7, 127. 

Brain Microvascular and Metabolic Adaptation to Proionged Mild Hypoxia... 

Figure 4 Development of ovine cerebral oxygen consumption. Brain metabolism increases with gestation, reaching a peak after birth before falling to adult levels. (Adapted from...

The rapid progress in proteomics and peptidomics during the last decade offers us new possibilities to study clinical aspects of disorders and diseases related to the brain [1], These strategies also offer new tools to follow chemical modifications and altered metabolic disturbances that may be indicative of pathophysiological adaptations related to environmental and psychosocial prolonged stress. These techniques can contribute to developments in the diagnostic and therapeutic fields of psychiatric... 

The literature contains numerous references to the use of MS/MS in the determination of new neuropeptides in identified cells of invertebrates (Bulau et al., 2004, for a recent example) and this technique is now being applied to in situ analysis of vertebrate tissues (Fournier et al., 2003). MS/MS is also used for studies of neuropeptide processing (Nilsson et al., 2001), pharmacokinetics of synthetic peptides (Mock et al., 2002), nonpeptide drug metabolism (Kamel et al., 2003), identification of peptides purified by immunoaffinity (Suresh Babu et al., 2004), and MALDI/MS/MS techniques adaptable to brain dialysis (Bogan and Agnes, 2004). 

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