SWAlexander
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Chris Armstrong and the Hunt for the Metabolic Underpinnings of ME/CFS
https://www.healthrising.org/blog/2021/10/17/chris-armstrong-chronic-fatigue-syndrome-metabolism/
Conclusion
Chris Armstrong and the 5th Open Medicine Foundation-funded research center in Australia are on something of a roll. Armstrong is continuing his focus on energy metabolism as he and his team try to understand the metabolic underpinnings of ME/CFS. If all goes well, we should learn more about why people with ME/CFS are so susceptible to crashes, why their cells may be starving (and what they are starving for), and if excess ammonia is wreaking havoc on cellular energy production. Plus, the eye study could potentially provide a cheap and accessible diagnostic test.
It probably comes as no surprise that excess ammonia can be a problem. When a dysfunctional liver fails to break down nitrogen, excess ammonia can produce neuroinflammation and encephalopathy. Nobody, until now, has applied the excess ammonia issue to cells.
Armstrong glommed onto his cellular ammonia accumulation hypothesis when metabolomic studies suggested that people with ME/CFS were using amino acids for fuel at a faster rate than healthy controls.
atp production in mitochondria
Most of the adenosine triphosphate (ATP) synthesized during glucose metabolism is produced in the mitochondria through oxidative phosphorylation. This is a complex reaction powered by the proton gradient across the mitochondrial inner membrane, which is generated by mitochondrial respiration.
https://pubmed.ncbi.nlm.nih.gov/16945388/
Amino acids are usually used for fuel at an elevated rate during a stress response or starvation. When you’re starving, for instance, your body will save your carbohydrates to make sure your brain and immune system are getting them. The rest of your body will use fats and amino acids in greater proportions. The long-term use of amino acids for energy will reduce digestive enzyme production and break down muscles and connective tissues.
For some reason, people with ME/CFS also appear to be preferentially turning to amino acids to power their cells. That presents a potential problem because amino acids have this pesky nitrogen atom attached to them that needs to be taken care of. The body usually eliminates the nitrogen from amino acids in a variety of “safe” forms, but the ME/CFS metabolomic studies are not finding as much of these “safe” forms as expected.
That suggests that all that nitrogen is being eliminated all right – but in “unsafe” forms such as ammonia or peroxynitrite – two highly reactive compounds that can wreak havoc in our cellular energy production system.
Why is ammonia highly toxic?
When excessive amounts of ammonia enter the central nervous system, the brain's defences are severely challenged. – A complex molecular chain reaction is triggered when the brain is exposed to excessive levels of ammonia. We have found that ammonia short-circuits the transport of potassium into the brain's glial cells.
What removes ammonia from the body?
Your body treats ammonia as a waste product, and gets rid of it through the liver. It can be added to other chemicals to form an amino acid called glutamine. It can also be used to form a chemical compound called urea. Your bloodstream moves the urea to your kidneys, where it is eliminated in your urine.
What does it mean when your breath smells like ammonia?
Chronic kidney disease (CKD) is one possible cause of having an ammonia taste in your mouth, sometimes called “ammonia breath.” Some people describe ammonia breath as having a metallic taste, while others have reported that it smells similar to urine.
Does high ammonia levels cause brain damage?
If your body can't process or eliminate ammonia, it builds up in the bloodstream. High ammonia levels in the blood can lead to serious health problems, including brain damage, coma, and even death. High ammonia levels in the blood are most often caused by liver disease.
What causes ammonia?
High ammonia levels sometimes point to either liver or kidney disease. But several other things can cause higher ammonia levels, like: Bleeding in your stomach, intestines, esophagus, or other parts of your body. Alcohol and drug use, including narcotics and medicines that take extra fluid out of your body (diuretics)
What are the symptoms of low ammonia?
Early symptoms may be mild and include:
Breath with a musty or sweet odor.
Changes in sleep patterns.
Changes in thinking.
Mild confusion.
Forgetfulness.
Personality or mood changes.
Poor concentration and judgment.
Worsening of handwriting or loss of other small hand movements.
(text in Italic from diff sources)
https://www.healthrising.org/blog/2021/10/17/chris-armstrong-chronic-fatigue-syndrome-metabolism/
Conclusion
Chris Armstrong and the 5th Open Medicine Foundation-funded research center in Australia are on something of a roll. Armstrong is continuing his focus on energy metabolism as he and his team try to understand the metabolic underpinnings of ME/CFS. If all goes well, we should learn more about why people with ME/CFS are so susceptible to crashes, why their cells may be starving (and what they are starving for), and if excess ammonia is wreaking havoc on cellular energy production. Plus, the eye study could potentially provide a cheap and accessible diagnostic test.
It probably comes as no surprise that excess ammonia can be a problem. When a dysfunctional liver fails to break down nitrogen, excess ammonia can produce neuroinflammation and encephalopathy. Nobody, until now, has applied the excess ammonia issue to cells.
Armstrong glommed onto his cellular ammonia accumulation hypothesis when metabolomic studies suggested that people with ME/CFS were using amino acids for fuel at a faster rate than healthy controls.
atp production in mitochondria
Most of the adenosine triphosphate (ATP) synthesized during glucose metabolism is produced in the mitochondria through oxidative phosphorylation. This is a complex reaction powered by the proton gradient across the mitochondrial inner membrane, which is generated by mitochondrial respiration.
https://pubmed.ncbi.nlm.nih.gov/16945388/
Amino acids are usually used for fuel at an elevated rate during a stress response or starvation. When you’re starving, for instance, your body will save your carbohydrates to make sure your brain and immune system are getting them. The rest of your body will use fats and amino acids in greater proportions. The long-term use of amino acids for energy will reduce digestive enzyme production and break down muscles and connective tissues.
For some reason, people with ME/CFS also appear to be preferentially turning to amino acids to power their cells. That presents a potential problem because amino acids have this pesky nitrogen atom attached to them that needs to be taken care of. The body usually eliminates the nitrogen from amino acids in a variety of “safe” forms, but the ME/CFS metabolomic studies are not finding as much of these “safe” forms as expected.
That suggests that all that nitrogen is being eliminated all right – but in “unsafe” forms such as ammonia or peroxynitrite – two highly reactive compounds that can wreak havoc in our cellular energy production system.
Why is ammonia highly toxic?
When excessive amounts of ammonia enter the central nervous system, the brain's defences are severely challenged. – A complex molecular chain reaction is triggered when the brain is exposed to excessive levels of ammonia. We have found that ammonia short-circuits the transport of potassium into the brain's glial cells.
What removes ammonia from the body?
Your body treats ammonia as a waste product, and gets rid of it through the liver. It can be added to other chemicals to form an amino acid called glutamine. It can also be used to form a chemical compound called urea. Your bloodstream moves the urea to your kidneys, where it is eliminated in your urine.
What does it mean when your breath smells like ammonia?
Chronic kidney disease (CKD) is one possible cause of having an ammonia taste in your mouth, sometimes called “ammonia breath.” Some people describe ammonia breath as having a metallic taste, while others have reported that it smells similar to urine.
Does high ammonia levels cause brain damage?
If your body can't process or eliminate ammonia, it builds up in the bloodstream. High ammonia levels in the blood can lead to serious health problems, including brain damage, coma, and even death. High ammonia levels in the blood are most often caused by liver disease.
What causes ammonia?
High ammonia levels sometimes point to either liver or kidney disease. But several other things can cause higher ammonia levels, like: Bleeding in your stomach, intestines, esophagus, or other parts of your body. Alcohol and drug use, including narcotics and medicines that take extra fluid out of your body (diuretics)
What are the symptoms of low ammonia?
Early symptoms may be mild and include:
Breath with a musty or sweet odor.
Changes in sleep patterns.
Changes in thinking.
Mild confusion.
Forgetfulness.
Personality or mood changes.
Poor concentration and judgment.
Worsening of handwriting or loss of other small hand movements.
(text in Italic from diff sources)
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