Why Inhibition of Spontaneous Motor Activity and Thought is so Significant; activation of the AMPK energy cellular regulation system

Reduction of spontaneous motor activity and of spontaneous thought is a major physical sign of an organism trying to conserve energy. This is why it occurs in graded form, when a person is ill, battling a cold or some other virus. A stuffed nose will affect breathing and affect how much air is exchanged. Feeling nauseous when ill , often causes lack of appetite and decreased eating and possible loss of weight, which further reduces energy availability.

……and if decreased energy availability is sever enough and lasts long enough without resolving, then the body has evolutionarily conserved mechanisms that cells can utilize to conserve energy until conditions improve, if the organism beats this virus and recovers its ability to eat and breathe normally or , if a slow process, suffers growing disability and eventual death.

It turns out, that we are learning more and more about how cellular pathways can be turned on and off depending on the energy sensing capabilities of the cells inside our bodies. And cells communicate with each other so as to maintain our internal chemical and physical conditions as adequate as is possible, given the physical conditions to which we are exposed [eg. viruses, diminished food availability, climate conditions, exposure to contaminants, etc…].

it is complicated, yet pretty straightforward.

ABSTRACT [Summary]

Living cells obtain energy either by oxidizing reduced compounds of organic or mineral origin or by absorbing light. Whichever energy source is used, some of the energy released is conserved by converting adenosine diphosphate (ADP) to adenosine triphosphate (ATP), which are analogous to the chemicals in a rechargeable battery. The energy released by the conversion of ATP back to ADP is used to drive most energy-requiring processes, including cell growth, cell division, communication and movement. It is clearly essential to life that the production and consumption of ATP are always maintained in balance, and the AMP-activated protein kinase (AMPK) is one of the key cellular regulatory systems that ensures this..……………………….. Once activated by energy imbalance or glucose lack, AMPK modifies many target proteins by transferring phosphate groups to them from ATP. By this means, numerous ATP-producing processes are switched on (including the production of new mitochondria) and ATP-consuming processes are switched off, thus restoring energy homeostasis. Keywords: AMP-activated protein kinase, AMP-activated protein kinase, mitochondria, energy homeostasis, cell signalling, adenosine triphosphate. Keeping the home fires burning: AMP-activated protein kinase D. Grahame Hardie J R Soc Interface. 2018 Jan; 15(138) : 20170774. Published online 2018 Jan 17. doi: 10.1098/rsif.2017.0774

Under difficult physical conditions, it seems that energy homeostasis, at the level of the cells and at the level of the whole organism, can be activated in order to conserve energy reversibly, until energy homeostasis can be restored under more favourable circumstances.

At a whole organism level, this will explain the reduction in voluntary movement seen in hypo-active delirium and in major depression or bipolar depressive attacks. It also explains the reduction in eating, both a consequence of feeling poorly, and an involuntary caloric reduction strategy which ironically can improves survival.

Notice that spontaneous motor activity is affected first, preserving the motor responses of the organism to external stimuli for as long as is possible, given the energy deficits. So the animal who is ill or starving will seem to be resting, mostly inactive, occasionally pacing…yet will be able to quickly run away if attacked.

Abstract

In mammals, AMPK is activated by an increasing cellular AMP:ATP ratio (which signifies a decrease in energy) caused by metabolic stresses that interfere with ATP production (eg, hypoxia) or that accelerate ATP consumption (eg, muscle contraction).…………… AMPK activation occurs by a dual mechanism that involves allosteric activation and phosphorylation by upstream kinases. Once activated, AMPK switches on catabolic pathways that generate ATP (eg, the uptake and oxidation of glucose and fatty acids and mitochondrial biogenesis) while switching off ATP-consuming, anabolic pathways (eg, the synthesis of lipids, glucose, glycogen, and proteins). In addition to the acute effects via direct phosphorylation of metabolic enzymes, AMPK has longer-term effects by regulating transcription. Am J Clin Nutr 2011 Apr;93(4):891S-6. doi: 10.3945/ajcn.110.001925.Epub 2011 Feb 16. Sensing of energy and nutrients by AMP-activated protein kinase D Grahame Hardie  PMID: 21325438 DOI: 10.3945/ajcn.110.001925

Major Metabolic stressors can switch catabolic and anabolic pathways on or off [ with AMPK] in order to balance the energy needs of the animal when oxygen and/or nutrients are limited or when the capacity to breath or eat is negatively affected by physical illness. Rest can conserve energy by reducing voluntary activity of the locomotor skeletal muscles during periods of illness. This is the reason for reduced spontaneous motor activity, motor activity utilizes more oxygen and more nutrients. In times of illness, the body is looking to conserve energy [oxygen and nutrients].

Abstract

Muscle catabolism is a fundamental response to severe stress, and the resulting amino acid efflux from muscle provides important precursors for protein synthesis in other parts of the body. The nature of this response (i.e. transport kinetics favoring efflux of amino acids from muscle) makes amelioration of the catabolic response of muscle with nutrition alone very difficult.   Curr Opin Clin Nutr Metab Care 2005 Jan;8(1):61-5. Regulation of skeletal muscle protein metabolism in catabolic states    Robert R Wolfe      10.1097/00075197-200501000-00009

So, in addition to reduced spontaneous motor activity and reduced spontaneous thought, Paula also had muscle wasting . A physical head to toe exam would have shown this but this, of course was not done, just as vital signs were not measured. No one realized that Paula had muscle wasting during her episode.

Paula’s respiratory rate would have shown possible respiratory acidosis from exacerbation of breathing difficulty in addition to her [hidden] broken breathing [described in other posts] and respiratory pump failure. Possible respiratory pump failure is a severe stress and would definitely explain her muscle wasting and loss of weight and loss of body condition.

What more is there to be said? One needs to actually look, investigate and measure in order to find even obvious physical signs. That is what doctors are supposed to do. Simply assuming a psychiatric diagnosis on the basis of a patient’s depressed behavior and experience of distress, will blind anyone to what the patient is unaware of, especially, if talking and listening to others talk is all psychiatrists do.

Abstract

Recent findings Acidosis has been shown to promote muscle protein catabolism by stimulating protein degradation and amino acid oxidation. This effect is achieved through up-regulation of the ubiquitin-proteasome pathway – one of the major enzyme systems for protein degradation. Recent studies in animals and humans have also shown that acidosis inhibits muscle protein synthesis. Little is known about the mechanisms by which acidosis depresses protein synthesis, or of the impact of alkalosis on protein metabolism. Summary Increasing evidence suggests that acidosis promotes muscle protein wasting by both increasing protein degradation and inhibiting protein synthesis. Control of muscle protein kinetics by acid-base balance.    Caso G   Garlick PJ    Current Opinion in Clinical Nutrition and Metabolic Care, 01 Jan 2005, 8(1):73-76    DOI:10.1097/00075197-200501000-00011  PMID: 15586003 

Dr Kraepelin’s measurements and findings of altered and depressed ventilation in thousands of unmedicated depressed patients and our discover of the same in Paula is very important and explains why Paula was so distressed and incompetent when she was sick. It explains a lot!

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