Pyruvate is an important chemical compound in biochemistry. It is the output of the metabolism of glucose known as glycolysis. One molecule of glucose breaks down into two molecules of pyruvate, which are then used to provide further energy, in one of two ways. Pyruvate is converted into acetyl-coenzyme A, which is the main input for a series of reactions known as the Krebs cycle (also known as the citric acid cycle or tricarboxylic acid cycle). Pyruvate is also converted to oxaloacetate by an anaplerotic reaction, which replenishes Krebs cycle intermediates; also, the oxaloacetate is used for gluconeogenesis. These reactions are named after Hans Adolf Krebs, the biochemist awarded the 1953 Nobel Prize for physiology, jointly with Fritz Lipmann, for research into metabolic processes. The cycle is also known as the citric acid cycle or tricarboxylic acid cycle, because citric acid is one of the intermediate compounds formed during the reactions.
Pyruvate is sold as a weight-loss supplement, though credible science has yet to back this claim. A systematic review of six trials found a statistically significant difference in body weight with pyruvate compared to placebo.
However, all of the trials had methodological weaknesses and the
magnitude of the effect was small. The review also identified adverse events associated with pyruvate such as diarrhea, bloating, gas, and increase in low-density lipoprotein (LDL) cholesterol. The authors concluded that there was insufficient evidence to support the use of pyruvate for weight loss.
There is also in vitro as well as in vivo evidence in hearts that pyruvate improves metabolism by NADH production stimulation and increases cardiac function.
The autonomic nervous system has three branches: the sympathetic nervous system, the parasympathetic nervous system and the enteric nervous system. Some textbooks do not include the enteric nervous system as part of this system. The sympathetic nervous system is often considered the "fight or flight"
system, while the parasympathetic nervous system is often considered
the "rest and digest" or "feed and breed" system. In many cases, both of
these systems have "opposite" actions where one system activates a
physiological response and the other inhibits it. An older
simplification of the sympathetic and parasympathetic nervous systems as
"excitatory" and "inhibitory" was overturned due to the many exceptions
found. A more modern characterization is that the sympathetic nervous
system is a "quick response mobilizing system" and the parasympathetic
is a "more slowly activated dampening system", but even this has exceptions, such as in sexual arousal and orgasm, wherein both play a role.
Although the ANS is also known as the visceral nervous system, the ANS is only connected with the motor side. Most autonomous functions are involuntary but they can often work in conjunction with the somatic nervous system which provides voluntary control.
Structure
Autonomic nervous system, showing splanchnic nerves in middle, and the vagus nerve as "X" in blue. The heart and organs below in list to right are regarded as viscera.
The autonomic nervous system is unique in that it requires a
sequential two-neuron efferent pathway; the preganglionic neuron must
first synapse onto a postganglionic neuron before innervating the target
organ. The preganglionic, or first, neuron will begin at the “outflow”
and will synapse at the postganglionic, or second, neuron's cell body.
The postganglionic neuron will then synapse at the target organ.
Sympathetic division
The sympathetic nervous system consists of cells with bodies in the lateral grey column from T1 to L2/3. These cell bodies are "GVE" (general visceral efferent) neurons
and are the preganglionic neurons. There are several locations upon
which preganglionic neurons can synapse for their postganglionic
neurons:
Paravertebral ganglia (3) of the sympathetic chain (these run on either side of the vertebral bodies)
Chromaffin cells of the adrenal medulla (this is the one exception to the two-neuron pathway rule: the synapse is directly efferent onto the target cell bodies)
These ganglia provide the postganglionic neurons from which innervation of target organs follows. Examples of splanchnic (visceral) nerves are:
Cervical cardiac nerves and thoracic visceral nerves, which synapse in the sympathetic chain
The parasympathetic nervous system consists of cells with bodies in one of two locations: the brainstem
(Cranial Nerves III, VII, IX, X) or the sacral spinal cord (S2, S3,
S4). These are the preganglionic neurons, which synapse with
postganglionic neurons in these locations:
These ganglia provide the postganglionic neurons from which innervations of target organs follows. Examples are:
The postganglionic parasympathetic splanchnic (visceral) nerves
The vagus nerve, which passes through the thorax and abdominal regions innervating, among other organs, the heart, lungs, liver and stomach
Sensory neurons
The sensory arm is composed of primary visceral sensory neurons found
in the peripheral nervous system (PNS), in cranial sensory ganglia: the
geniculate, petrosal and nodose ganglia, appended respectively to
cranial nerves VII, IX and X. These sensory neurons monitor the levels
of carbon dioxide, oxygen and sugar in the blood, arterial pressure and
the chemical composition of the stomach and gut content. They also
convey the sense of taste and smell, which, unlike most functions of the
ANS, is a conscious perception. Blood oxygen and carbon dioxide are in
fact directly sensed by the carotid body, a small collection of
chemosensors at the bifurcation of the carotid artery, innervated by the
petrosal (IXth) ganglion.
Primary sensory neurons project (synapse) onto “second order” visceral
sensory neurons located in the medulla oblongata, forming the nucleus of
the solitary tract (nTS), that integrates all visceral information. The
nTS also receives input from a nearby chemosensory center, the area
postrema, that detects toxins in the blood and the cerebrospinal fluid
and is essential for chemically induced vomiting or conditional taste
aversion (the memory that ensures that an animal that has been poisoned
by a food never touches it again). All this visceral sensory information
constantly and unconsciously modulates the activity of the motor
neurons of the ANS.
Innervation
Autonomic nerves travel to organs throughout the body. Most organs receive parasympathetic supply by the vagus nerve and sympathetic supply by splanchnic nerves. The sensory part of the latter reaches the spinal column at certain spinal segments. Pain in any internal organ is perceived as referred pain, more specifically as pain from the dermatome corresponding to the spinal segment.
Autonomic nervous supply to organs in the human body
Motor neurons of the autonomic nervous system are found in
‘’autonomic ganglia’’. Those of the parasympathetic branch are located
close to the target organ whilst the ganglia of the sympathetic branch
are located close to the spinal cord.
The sympathetic ganglia here, are found in two chains: the
pre-vertebral and pre-aortic chains. The activity of autonomic
ganglionic neurons is modulated by “preganglionic neurons” located in
the central nervous system. Preganglionic sympathetic neurons are
located in the spinal cord, at the thorax and upper lumbar levels.
Preganglionic parasympathetic neurons are found in the medulla oblongata
where they form visceral motor nuclei; the dorsal motor nucleus of the
vagus nerve; the nucleus ambiguus, the salivatory nuclei, and in the sacral region of the spinal cord.
Function
Function of the autonomic nervous system
Sympathetic and parasympathetic divisions typically function in
opposition to each other. But this opposition is better termed
complementary in nature rather than antagonistic. For an analogy, one
may think of the sympathetic division as the accelerator and the
parasympathetic division as the brake. The sympathetic division
typically functions in actions requiring quick responses. The
parasympathetic division functions with actions that do not require
immediate reaction. The sympathetic system is often considered the "fight or flight" system, while the parasympathetic system is often considered the "rest and digest" or "feed and breed" system.
However, many instances of sympathetic and parasympathetic
activity cannot be ascribed to "fight" or "rest" situations. For
example, standing up from a reclining or sitting position would entail
an unsustainable drop in blood pressure if not for a compensatory
increase in the arterial sympathetic tonus. Another example is the
constant, second-to-second, modulation of heart rate by sympathetic and
parasympathetic influences, as a function of the respiratory cycles. In
general, these two systems should be seen as permanently modulating
vital functions, in usually antagonistic fashion, to achieve homeostasis.
Higher organisms maintain their integrity via homeostasis which relies
on negative feedback regulation which, in turn, typically depends on the
autonomic nervous system. Some typical actions of the sympathetic and parasympathetic nervous systems are listed below.
Target organ/system
Parasympathetic
Sympathetic
Digestive system
Increase peristalsis and amount of secretion by digestive glands
Decrease activity of digestive system
Liver
No effect
Causes glucose to be release to blood
Lungs
Constricts bronchioles
Dilates bronchioles
Urinary bladder/ Urethra
Relaxes sphincter
Constricts sphincter
Kidneys
No effects
Decrease urine output
Heart
Decreases rate
Increase rate
Blood vessels
No effect on most blood vessels
Constricts blood vessels in viscera; increase BP
Salivary and Lacrimal glands
Stimulates; increases production of saliva and tears
Inhibits; result in dry mouth and dry eyes
Eye (iris)
Stimulates constrictor muscles; constrict pupils
Stimulate dilator muscle; dilates pupils
Eye (ciliary muscles)
Stimulates to increase bulging of lens for close vision
Inhibits; decrease bulging of lens; prepares for distant vision
Adrenal Medulla
No effect
Stimulate medulla cells to secrete epinephrine and norepinephrine
Sweat gland of skin
No effect
Stimulate to produce perspiration
Sympathetic nervous system
Promotes a fight-or-flight response, corresponds with arousal and energy generation, and inhibits digestion
The parasympathetic nervous system has been said to promote a "rest
and digest" response, promotes calming of the nerves return to regular
function, and enhancing digestion. Functions of nerves within the
parasympathetic nervous system include:
Dilating blood vessels leading to the GI tract, increasing the blood flow.
Constricting the bronchiolar diameter when the need for oxygen has diminished
Constriction of the pupil and contraction of the ciliary muscles, facilitating accommodation and allowing for closer vision
Stimulating salivary gland secretion, and accelerates peristalsis, mediating digestion of food and, indirectly, the absorption of nutrients
Sexual. Nerves of the peripheral nervous system are involved in the erection of genital tissues via the pelvic splanchnic nerves 2–4. They are also responsible for stimulating sexual arousal.
Enteric nervous system
The enteric nervous system is the intrinsic nervous system of the gastrointestinal system. It has been described as "the Second Brain of the Human Body". Its functions include:
Sensing chemical and mechanical changes in the gut
A
flow diagram showing the process of stimulation of adrenal medulla that
makes it release adrenaline, that further acts on adrenoreceptors,
indirectly mediating or mimicking sympathetic activity.
At the effector organs, sympathetic ganglionic neurons release noradrenaline (norepinephrine), along with other cotransmitters such as ATP, to act on adrenergic receptors, with the exception of the sweat glands and the adrenal medulla:
Acetylcholine
is the preganglionic neurotransmitter for both divisions of the ANS, as
well as the postganglionic neurotransmitter of parasympathetic neurons.
Nerves that release acetylcholine are said to be cholinergic. In the
parasympathetic system, ganglionic neurons use acetylcholine as a
neurotransmitter to stimulate muscarinic receptors.
At the adrenal medulla, there is no postsynaptic neuron. Instead the presynaptic neuron releases acetylcholine to act on nicotinic receptors. Stimulation of the adrenal medulla releases adrenaline
(epinephrine) into the bloodstream, which acts on adrenoceptors,
thereby indirectly mediating or mimicking sympathetic activity.
Caffeine effects
Caffeine
is a bio-active ingredient found in commonly consumed beverages such as
coffee, tea, and sodas. Short-term physiological effects of caffeine
include increased blood pressure and sympathetic nerve outflow. Habitual
consumption of caffeine may inhibit physiological short-term effects.
Consumption of caffeinated espresso increases parasympathetic activity
in habitual caffeine consumers; however, decaffeinated espresso inhibits
parasympathetic activity in habitual caffeine consumers. It is possible
that other bio-active ingredients in decaffeinated espresso may also
contribute to the inhibition of parasympathetic activity in habitual
caffeine consumers.
Caffeine is capable of increasing work capacity while individuals
perform strenuous tasks. In one study, caffeine provoked a greater
maximum heart rate while a strenuous task was being performed compared
to a placebo. This tendency is likely due to caffeine's ability to
increase sympathetic nerve outflow. Furthermore, this study found that
recovery after intense exercise was slower when caffeine was consumed
prior to exercise. This finding is indicative of caffeine's tendency to
inhibit parasympathetic activity in non-habitual consumers. The
caffeine-stimulated increase in nerve activity is likely to evoke other
physiological effects as the body attempts to maintain homeostasis.
The effects of caffeine on parasympathetic activity may vary
depending on the position of the individual when autonomic responses are
measured. One study found that the seated position inhibited autonomic
activity after caffeine consumption (75 mg); however, parasympathetic
activity increased in the supine position. This finding may explain why
some habitual caffeine consumers (75 mg or less) do not experience
short-term effects of caffeine if their routine requires many hours in a
seated position. It is important to note that the data supporting
increased parasympathetic activity in the supine position was derived
from an experiment involving participants between the ages of 25 and 30
who were considered healthy and sedentary. Caffeine may influence
autonomic activity differently for individuals who are more active or
elderly.
