Lack of magnesium
How does a lack of magnesium induce a deficiency in mitochondrial energy at the end of the process?
I’ve been reading a RP letter recently and I wanted afterwards to go deeper in the PKC system (Protein Kinase C) to connect the dots. (1)
Nearly every reader here knows the impact of PUFA on metabolism. And the interdependence and the ripple effect between excess estrogens and adipocyte cells (though AA cascade when we are stressed).
When we have difficulty in maintaining an adequate energy production, whatever the cause may be (e.g. diabetes, hypothyroidism, colopathy, etc.), a deficit produces an alarm state, causing increased production of adrenalin and cortisol. (2) (Derived from the "fight-or-flight" response, a protective survival process). These stress hormones trigger the release of stored energy from the liver (glycogenolysis) and fat tissue (lipolysis). Thus, adrenalin mobilizes fat from storage, and these free fatty acids are often going to create a chronic problem.
Metabolic Shift
During stress, the hormones adrenaline (epinephrine) and cortisol shift the body's energy focus from glycolysis (using glucose for energy) towards lipolysis (breaking down stored fats for energy). However, reduced reliance on glycolysis is not completely shut down; its relative importance is diminished as the body prioritizes fat breakdown for energy. Big advantage of our specie on the animal reign (enable to quickly mobilize stored energy reserves for a long time).
Estrogen and PUFA activate the PKC system
I cite RP:
“Estrogen and the polyunsaturated fatty acids (PUFA), linoleic and linolenic acid, alike activate the protein kinase C (PKC) system of cellular activation. Many of the functions of PUFA are similar to the functions of estrogen (e.g., antagonism to thyroid function, promotion of age pigment/lipofuscin), so this information showing that they both act similarly on the same basic regulatory pathway is important.
Estrogen increases secretion of growth hormone (GH; it's closely associated with prolactin, also increased by estrogen), and GH causes an increase in free fatty acids in the blood. Estrogen promotes iron retention, so it sets the stage for oxidative stress. At least in some systems, both estrogen and PUFA promote the entry of calcium into the cell.” (1)
In diabetes, there is a generalized excess activation of the PKC system (protein kinase C). (…)
Protein Kinase C system (PKC)
What is the role of PKC system and its impact on energy?
In short: PKC is a key player in cellular energy regulation, influencing mitochondrial function, energy sensing, neurotransmitter release, and other energy-related processes. By modulating these processes, PKC helps cells maintain energy balance and respond to changes in energy availability.
PKC is also intertwined with other energy-signaling processes (AMPK) and neurotransmitters.
PKC system in details
Here's a more detailed look at PKC's impact on energy:
Mitochondrial Function:
• PKC signaling can influence mitochondrial function by regulating enzymes involved in oxidative phosphorylation, the process by which mitochondria generate ATP.
• For example, PKC can regulate pyruvate dehydrogenase (PDH) and cytochrome c oxidase (Complex IV), which are critical for cellular energy production.
• PKC also plays a role in mitochondrial dynamics, which is important for maintaining healthy mitochondria and efficient energy production.
Energy Sensing and Signaling:
• PKC can phosphorylate AMPK, an enzyme that is activated by cellular energy depletion.
• This phosphorylation can affect AMPK's activity, which in turn influences cellular processes that regulate energy balance.
• By interacting with AMPK, PKC can help cells respond to changes in energy levels and maintain homeostasis.
Neurotransmitter Release and Energy:
• PKC is involved in regulating neurotransmitter release, which requires energy for the process of exocytosis (releasing neurotransmitters from vesicles).
• By modulating the proteins involved in synaptic vesicle exocytosis, PKC can impact the energy demands of neuronal signaling.
Other Energy-Related Processes:
• PKC can influence various other cellular processes related to energy, such as the opening and closing of the mitochondrial permeability transition pore (MPTP), which affects mitochondrial function and energy production.
• PKC can also affect the activity of proteasomes, which are involved in protein degradation and cellular energy balance.
In summary: PKC is a key player in cellular energy regulation, influencing mitochondrial function, energy sensing, neurotransmitter release, and other energy-related processes. By modulating these processes, PKC helps cells maintain energy balance and respond to changes in energy availability.
Sources and References
Diabetes, scleroderma, oils and hormones”. 2006
raypeat.com
The Role of Protein Kinase C During the Differentiation of Stem and Precursor Cells into Tissue Cells - doi: 10.3390/biomedicines12122735 Biomedicines 2024
AA cascade
Cascade AA Cox Lox P450 03.gif
The AA cascade explained when there is a discharge of FFA due to stress. We already know the deleterious effects of excess PUFA.
When you're stressed, your body releases certain hormones that trigger your cells to break down fats stored in the membranes. One of the fats released is called arachidonic acid (AA), which comes from a type of fat known as PUFA.
Once AA is free in the body, it acts like fuel for inflammation. It gets turned into other substances (prostaglandins) that tell the body to create swelling, pain, and heat — all part of the "inflammatory response." While this can be helpful short-term (like in healing), too much of it keeps the body in a state of constant low-level inflammation (especially from diets high in omega-6).
So, during stress, your body’s release of AA can make things worse if you already have a lot of these fats stored. That’s part of why people say excess PUFA can have harmful effects, especially over time.
Prostaglandins (PGE) and their link to excess omega-6 (ALA) in the AA cascade:
When we eat a lot of omega-6 fats — especially from things like seed, corn or soy oils — our bodies convert them into arachidonic acid (AA). This is especially true with a type of omega-6 fat called linoleic acid (LA, a type of omega-6) — not to be confused with alpha-linolenic acid (ALA, a type of omega-3).
Once there's a buildup of AA in our cells – we don't use / need much PUFA, stress can trigger the release of AA into the body. That’s where things take a turn: AA gets turned into compounds like prostaglandins (especially PGE2).
Prostaglandins (PGE) are like chemical messengers that tell the body to create inflammation. They're useful in small amounts for healing and repair, but when there’s too much AA around, you get too much PGE2, which causes chronic inflammation, swelling, and even pain.
This inflammation signals the body that something’s wrong — which ironically increases stress levels further. It becomes a vicious cycle:
More omega-6 → more AA → more PGE2 → more inflammation → more stress.
That’s one reason people are concerned about eating too much omega-6, especially from processed foods. It overloads this system and keeps your body in a kind of "fight mode" all the time.
Cascade AA & prostaglndines.jpg
