Metabolic activity, brain

Brain metabolic activity is very high (a major component of which is the activity of the Na+-K+ ATPase) interference with the blood supply or O2 delivery will have prompt consequences. Such events are called strokes they are the third most common cause of death in developed countries. 

In addition, adenosine is implicated in sleep regulation. During periods of extended wakefulness, extracellular adenosine levels rise as a result of metabolic activity in the brain, and this increase promotes sleepiness. During sleep, adenosine levels fall. Caffeine promotes wakefulness by blocking the interaction of extracellular adenosine with its neuronal receptors. ... 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

Permethrin, a pyrethrin pesticide, decreased the inhibition of brain cholinesterase activity by methyl parathion, but methyl parathion decreased the LD50 of permethrin when the two pesticides were simultaneously administered to rats (Ortiz et al. 1995). The potentiation of permethrin lethality may be due to the inhibition by methyl parathion of carboxylesterase, which metabolizes permethrin. 

Miller, K.J. Anderholm, D.C. and Ames, M.M. Metabolic activation of the serotonergic neurotoxin para-chloroamphetamine to chemically reactive intermediates by hepatic and brain microsomal preparations. Biochem Pharmacon>5 mi- lA2, 1986. 

Volkow ND, Gillespie H, Mullani N, Tancredi L, Grant C, Ivanovic M, Hollister L. Cerebellar metabolic activation by delta-9-tetrahydrocannabi-nol in human brains. A study with positron emission tomography and 18F-2-deoxy-2-fluoro-D-glucose. Psychiat Res 1991 40 69-80. 

Certain enzymes shown to be present in myelin could be involved in ion transport. Carbonic anhydrase has generally been considered a soluble enzyme and a glial marker but myelin accounts for a large part of the membrane-bound form in brain. This enzyme may play a role in removal of carbonic acid from metabolically active axons. The enzymes 5 -nucleotidase and Na+, K+-ATPase have long been considered specific markers for plasma membranes and are found in myelin at low levels. The 5 -nucleotidase activity may be related to a transport mechanism for adenosine, and Na+, K+-ATPase could well be involved in transport of monovalent cations. The presence of these enzymes suggests that myelin may have an active role in ion transport in and out of the axon. In connection with this hypothesis, it is of interest that the PLP gene family may have evolved from a pore-forming polypeptide [9],... 

We can hardly escape the realization that brain metabolism is both extremely active and extremely important for the well-being and intellectual activity of the organism, and that unless it proceeds in a normal fashion mental health cannot exist. 

Ghersi-Egea JF Minn A, Siest G (1988) A new aspect of the protective functions of the blood-brain barrier Activities of four drug-metabolizing enzymes in isolated brain microvessels. Life Sci 42 2515-2523... 

SPMD sample extracts, e.g., certain organochlorine pesticides (OCPs), are known to inhibit cholinesterase activity. Therefore, these results were not unexpected. However, it was surprising that a similar response was not observed with brain cholinesterase activity. It is possible that brain cells can more readily metabolize the chemicals, that the chemicals did not pass the brain blood barrier or that the effects occurred earlier in the exposure period, effectively allowing the activity to recover. Considering the numerous neurotoxic chemicals potentially entering aquatic ecosystems or present as airborne vapor phase chemicals, the neurotoxic mode of action related to exposure to contaminants is of increasing interest. Evidence presented in this work demonstrate that SPMDs concentrate members of this class of toxicants. 

McNamara D, Larson DM, Rapoport SI, Soncrant TT. (1990). Preferential metabolic activation of subcortical brain areas by acute administration of nicotine to rats. J Cereb Blood Flow Metab. 10(1) 48-56. 

Basal brain activity and regional brain activation levels are not the same in males and females. Fallon et al. (2005) studied brain metabolism with 2-[ F] fluoro-2-deoxy-D-glucose and positron emission tomography (FDG-PET) in male and female... 

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