Polyamines
Polyamines (putrescine, spermidine, spermine) are small, positively charged molecules the body makes from amino acids in response to stress, injury, and osmotic imbalance. In small, transient amounts they support healing. Sustained high levels drive cell division, altered gene expression, nerve injury, and cancer growth.
Function/Mechanism of Action
[edit]Ornithine decarboxylase (ODC) makes the polyamines from ornithine. Excess water in the tissue (hypotonicity), estrogen, and stress all activate ODC.[1]
An excess of water stimulates cell division, and an important mechanism in producing that effect is the increased production of polyamines by the enzyme ornithine decarboxylase. This enzyme is activated by an excess of water (hypotonicity), by estrogen, and by stress.
Polyamines are small and positively charged, so they bind DNA-associated histone proteins directly and shift which genes are read, a stress-driven layer on top of the "histone code."[3] The same positive charge lets them cross the blood-brain barrier that excludes most proteins, so they concentrate in the brain and contribute to nerve excitation and excitotoxicity, and at excess they can contribute to breakdown of the barrier itself.[4]
Protein catabolism disposes of amino-acid nitrogen one of two ways: as urea, or as polyamines. Adequate CO2/bicarbonate pushes ammonia toward urea synthesis and away from polyamine formation; poor respiration and stress push it the other way.[5]
Clinical significance
[edit]Polyamines are elevated in cancer tissue and in cancer patients' urine. Therapies to block their synthesis are able to stop growth of prostate, bowel, and breast cancers, and urinary/red-cell polyamine levels are used as disease markers.[6][7] In a randomized trial, the polyamine-synthesis inhibitor difluoromethylornithine combined with sulindac cut colorectal adenoma recurrence to 11-21% versus 34-50% with placebo, depending on ODC1 genotype.[8] They also contribute to nerve injury, seizure sensitization, and blood-brain barrier disruption.[4]
Direct, optimal effects of polyamines are protective and support healing. Excessive, prolonged polyamine exposure, or exposure without maintained cellular energy, turns the same molecules harmful, promoting the "bystander effect" around injured or irradiated tissue and contributing to tumor formation.[9]
Dietary sources
[edit]Estrogen, stress, and injury before slaughter raise the polyamine content of meat; storage/aging after slaughter raises it further as glycogen depletes and anaerobic protein breakdown accelerates.[1] Stressed, stored vegetables show the same rise. Because polyamines, estrogen, and PUFA intensify each other's neurotoxic and carcinogenic effects, those three types of substance should be considered as a functional unit when making food choices.[10]
Protective factors
[edit]- Adequate CO2/bicarbonate, directs ammonia to urea instead of polyamines; anti-edema, anti-seizure, anticancer
- Magnesium, niacin, vitamin A, aspirin
- Procaine and other local anesthetics
- Caffeine, in some circumstances
- A non-irritating diet that limits endotoxin; gelatin is low in tryptophan and methionine, the amino acids that feed polyamine formation[11]
See also
[edit]References
[edit]- ↑ 1.0 1.1 Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com, 2014.
- ↑ Meat physiology, stress, and degenerative physiology., Ray Peat newsletter
- ↑ Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com, 2014.
- ↑ 4.0 4.1 Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com, 2014.
- ↑ Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com, 2014.
- ↑ Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com, 2014.
- ↑ Luk GD, Baylin SB, "Ornithine decarboxylase as a biologic marker in familial colonic polyposis," New England Journal of Medicine. 1984;311(2):80-3. PMID 6738598.
- ↑ Zell JA, McLaren CE, Chen WP, Thompson PA, Gerner EW, Meyskens FL, "Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients," Journal of the National Cancer Institute. 2010;102(19):1513-6. PMID 20798393.
- ↑ Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com, 2014.
- ↑ Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com, 2014.
- ↑ Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com, 2014.