The Role of Acetylation in Gene Expression

Pantothenic acid is vitamin B5. You use it to make coenzyme A, a molecule that is central to energy metabolism, most famous for forming acetyl CoA, which lies at the intersection of all anabolic (building up) and catabolic (breaking down) reactions.

Alex Leaf and I team up again, this time to tackle B5.

This is what happens when you don’t have enough:

• You get fatigue apathy, discomfort, uneasiness, or pain.
• You get numbness and tingling in the hands and feet.
• You may get depressed, quarrelsome, childish, or want to spend all day in bed.
• Your pulse gets higher than you’d expect after minor exertion.
• Your sleep gets trashed.
• You get muscle cramps and abdominal cramps, you fart more, and when things get real bad you might throw up.

Much of this can be explained by pantothenic acid’s role in working all of this magic:

• We use it break down fat, protein, and carbohydrate for energy.
• We use it to synthesize fatty acids, ketones, and cholesterol.
• We use it to synthesize all of the steroid hormones, including the sex hormones, the glucocorticoids that regulate blood sugar, and the mineralcorticoids that regulate electrolyte balance and blood pressure.
• We use it to regulate our use of iron properly, including preventing its accumulation in the brain, where it can cause neurological damage.
• We use it to make melatonin, which tells our body it’s time to sleep.
• We use it to make acetylcholine, a neurotransmitter involved in learning, memory, and cognitive performance during periods of sustained, focused attention.
• We use it to make mucin, which lubricates the eyes, ears, nose, mouth, vagina, penis, and internal organs.
• We use it to regulate the fasting/feeding cycle by flipping on the genes for autophagy during fasting and flipping on the genes for repair and antioxidant defense during feeding.
• We use it for quite a few other things too, like the detoxification of some drugs; the synthesis of hemoglobin to prevent anemia; switching on the urea cycle to help us burn protein for energy cleanly; using folate to synthesize DNA, all the major vitamin-derived carriers in the system of energy metabolism, and glycine, an amino acid that acts as a calming, sleep-promoting neurotransmitter, stabilizes blood sugar, and supports collagen synthesis to make your bones strong and your skin smooth.

Burning fat only requires 20% more B5 than burning carbs, which is small compared to how these macros affect riboflavin requirements, However, under conditions of stress you can burn carbohydrate without any B5 at all and you cannot do that with fat. In mice with severe deficiencies of coenzyme A, ketogenic diets dramatically worsen the neurological effects of deficiency.

Although pantothenic acid is named for its presence everywhere and in everything using the Greek word “pantos,” and the common dogma is that no one is deficient, Alex and I make the case in this two-part podcast that suboptimal pantothenic acid status might just be the norm.

And the crazy thing? Official recommendations suggest we only need about 5 milligrams per day. In the podcast we discuss why some people might need GRAMS per day.

Plus, why the FOOD forms might be superior to anything you can get in any supplements on the market.

In part 2, to be released on July 5, we’ll cover how to get pantothenic acid in foods, blood tests, and supplements.

This episode is brought to you by Ancestral Supplements' "Living" Collagen. Our Native American ancestors believed that eating the organs from a healthy animal would support the health of the corresponding organ of the individual. Ancestral Supplements has a nose-to-tail product line of grass-fed liver, organs, "living" collagen, bone marrow and more... in the convenience of a capsule. For more information or to buy any of their products, go to https://chrismasterjohnphd.com/ancestral

In this episode you will find all of the following and more:

00:37 Cliff Notes

14:02 Symptoms of experimentally induced pantothenic acid deficiency

15:57 It is thought that pantothenic acid deficiency doesn’t occur naturally.

18:59 Experiments inducing pantothenic acid deficiency

26:06 Signs and symptoms of suboptimal pantothenic acid status

26:54 Is there pantothenic acid toxicity?

30:52 Hypothetical problems of taking high doses of pantothenic acid

31:53 What pantothenic acid is

35:28 Comparisons to niacin and riboflavin

37:14 Roles of coenzyme A

46:02 Roles of 4’-phosphopantetheine

48:12 Burning fat requires 20% more vitamin B5 than burning carbohydrate; and why in the context of severe deficiency of B5 or impairment in the metabolism of B5 a high-fat diet could have devastating consequences.

53:09 The importance of the ratio of acetyl-CoA to free CoA in regulating many metabolic pathways

01:01:02 There are metabolic disorders, such as fatty acid oxidation disorders, that compromise the pool of coenzyme A.

01:03:03 Synthesis of coenzyme A

01:06:47 How coenzyme A synthesis is regulated

01:11:38 Degradation of coenzyme A

01:15:44 The physiology of pantothenic acid absorption

01:25:29 A 2015 paper showed that 4’-phosphopantetheine can cross cell membranes via passive diffusion.

01:29:00 The physiology of pantothenic acid transport in the blood

01:32:11 Cellular uptake of pantothenic acid from the blood

01:33:21 Tissue distribution of pantothenic acid

01:36:00 There may be a particularly high need for pantothenic acid in adolescence.

01:37:01 Mothers actively transfer pantothenic acid to their fetuses and into their milk at their own expense.

01:39:29 Pharmacokinetics of supplementation

01:48:20 A case for why food is superior to supplements for vitamin B5

01:52:41 Inborn errors of coenzyme A metabolism include pantothenate kinase-associated neurodegeneration (PKAN).

Access the show notes, transcript, and comments here:

https://chrismasterjohnphd.substack.com/p/064-pantothenic-acid-part-1-what