The brain is the control center of all physical and intellectual activity in the body. Ten billion different cells, with millions upon millions of neurons, forming connections several hundred times more numerous than the world's population. At the age of thirty cell units die and are never replaced again, thus beginning an inexorable process that becomes more and more acute in the elderly.
The brain normally receives 15-20% of the body's total blood supply and uses 15-20% of the body's totaled inhaled oxygen. The brain must use this oxygen, along with glucose to produce and use 15-20% of the body's total ATP energy. Unlike most other cells, which can burn fat or sugar (glucose) for their energy needs, neurons can only burn glucose under normal conditions, they typically consume 50% of the total blood glucose. Unlike liver and muscle cells, which can store large amounts of sugar as glycogen, neurons can only store at most a minute or two worth of glucose, and so are dependent upon a continuous and uninterrupted blood supply to maintain normal energy metabolism and avoid injury or death.
Most other cells (except heart and skeletal muscle cells) reproduce continually throughout a lifetime yet after the brain reaches a full complement of neurons (birth to 2 years of age), neurons never reproduce, they are an irreplaceable essential of life.
Under normal conditions of adequate oxygen supply, neurons convert glucose into energy (ATP) through a 3-phase process.
The first phase occurs in the cytoplasm of the cell (the gel-like stuff between the nucleus and outer cell membrane), and is called 'aerobic [oxygen using] glycolysis.' As each molecule of glucose is metabolized through aerobic glycolysis, two molecules of ATP are produced.
In addition, two other by-products result which is used to make further ATP in the next two phases of energy production.
Aerobic glycolysis produces two molecules of NADH for each molecule of glucose burned. The NADH is then transported to the mitochondria, where it serves as a fuel in the third phase of energy metabolism- the electron transport side chain (ETSC). Each NADH run through the ETSC, with adequate oxygen, produces 3 molecules of ATP. Eventually, through the successful interaction of aerobic glycolysis, the Kreb's/ citric acid cycle, and the ETSC, a single molecule of glucose can yield a maximum of 38 molecules of ATP bio-energy, assuming adequate oxygen for both glycolysis and mitochondrial 'respiratory' metabolism.
When neurons are under-supplied with oxygen, however, different forms of sugar burning occurs- anaerobic (without oxygen) glycolysis.
For each molecule of glucose burned, anaerobic glycolysis yields two molecules of ATP. However, instead of producing the valuable Kreb's cycle fuel, pyruvic acid, anaerobic glycolysis produces the somewhat toxic waste product, lactic acid. And anaerobic glycolysis yields no bonus of NADH to be converted to ATP through the ETSC. And with inadequate oxygen, mitochondrial metabolism proceeds poorly, it at all.
Thus anaerobic glycolysis produces a total of only two ATP's for each glucose burned.
In other words, when glucose brain fuel is burned without adequate oxygen, it produces only 5% as much ATP energy as when glucose is burned with adequate oxygen!
There are 3 main uses for ATP inside neurons:
Since neurons don't reproduce and must last a lifetime, they are continually expending energy to repair or replace various cell components- cell membrane segments, microtubules, mitochondria, etc.
Neurons also use ATP, to produce, transport, package, secrete and reuptake neurotransmitters, which provide cell to cell communication. And massive amounts of ATP are necessary to facilitate the frequent discharges of electrical energy from the receiving end of the neuron- the dendrites- through the cell body, where signal processing occurs, and down the transmitting end- the axon. For this electrical process to occur there must be a rapid and continuous exchange of sodium and potassium ions back and forth across the neuronal membranes.
This exchange process depends on sodium-potassium pumps, powered by sodium-potassium ATPase enzyme systems.
Some physiologists estimate as much as 45% of a neuron's ATP may be used to power the sodium-potassium pumps.
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