What is the problem 1 - The blocked kynurenine pathway

Introduction

The pig (Sus scrofa) is an excellent biomedical model as it is very similar to humans in terms of size, anatomy, physiology, metabolism, pathology and pharmacology. Alan Archibald, Professor of Medicine and Veterinary Science at the University of Edinburgh's Faculty of Medicine, believes that pig studies provide the best results in all cases (Alan Archibald et al; 2020).
Nowadays, there are more and more serious health problems in humans and animals. The increasing frequency of these problems and the new diseases are often not associated with the changed environmental factors. Genetically modified feed and food crops and the effects of additives used in feed and food in recent decades have not been sufficiently investigated.
Experience in animal husbandry over the last four decades is divided into two parts. Until around 1996, feed mixtures were made from non-genetically modified feedstuffs. They contained no free amino acids, fermentation by-products or so-called single cell proteins (SCP). After the year 2000, GMO feed plants and free amino acids increased in animal production.
Farm animals and humans have many similar effects in their diet:

• Cultivation of plants in the same soil with the same technology
• Free amino acids (produced by GM bacteria and used as additives in animal feed and processed foods)
• GMO feed materials and GMO food plants.

It is no coincidence that Alan Archibald, Professor of Medicine and Veterinary Medicine at the University of Edinburgh, emphasises the need for close links between human and veterinary sciences in his work.
The mitochondria of pigs function in a similar way to those of humans. The hormone and enzyme system is the same and the immune system is very similar. The gastrointestinal and microbiological problems of humans are also typical of pigs. There are many similarities between pigs and humans, but one crucial difference is the generation interval. It is 14 months in pigs and 25 years in humans. Human mothers give birth to 1-4 children in their lifetime, whereas sow mothers can have up to 100 offspring. This time saving and the fact that thousands of animals can eat the same feed composition on a pig farm allow important conclusions to be drawn.

Effects of modern animal feed on livestock and indirectly on humans

The problem of tryptophan-amino acid metabolism and the resulting lack of nicotinic acid (Niacin) occurs in various forms in animals fed industrially produced feed.
Niacin deficiency leads to insufficient energy production in the cells (through the production of NAD+). In the last 10 to 15 years, an increase in skin lesions previously unknown has been observed in pigs fed industrial feed. The lesions and pellagra symptoms caused by niacin deficiency are scaly inflammations of the skin, neck and back. Necrosis of the upper skin layer and ulceration of the tongue and oral mucosa are common. In addition to the hyperkeratotic symptoms on the back and spinal cord, a bluish-green pigmented patch may appear on the back. The lesions affect the epithelial cells of the skin. The same applies to the epithelial cells of the mucous membranes of the digestive tract. Necrotising and ulcerating enteritis may also occur.
The researcher who investigated pellagra in humans was the Hungarian-born physician József Goldberger (1874-1929), who worked in America and was a doctor with the US Public Health Service in New York.
He hypothesised that the skin disease was not infectious, but diet-related. According to Goldberger, pellagra is a so-called 4-D disease: dermatitis - inflammation of the skin, diarrhoea, dementia and death. In addition to skin pellagra in sows, which is caused by a lack of nicotinic acid, piglets suffer damage to the epithelial cells of the intestinal mucosa during development in the womb, known as PFTS syndrome. In these cases, the piglets are born with damage to the stomach and intestinal mucosa and atrophy of the villi.

The blocked urea cycle

A typical symptom in pigs is foaming at the mouth as a sign of ammonia poisoning. This means that the urea cycle in the liver is not working. The blood shows high ammonia levels and the blood-brain barrier (BBB) allows ammonia to enter the spinal fluid, blocking the motor cells and preventing the animal from swallowing.
There are two reasons for this:

• The first is the lysineArginine-antagonism (which leads to a local arginine deficiency).
• A localised arginine deficiency impairs the function of the urea cycle.
• Another cause is the so-called "Hans Adolf Krebs phenomenon".
• The Szent-Györgyi Krebs cycle, the last phase of biological oxidation, degradation (the most efficient process of energy production), does not function properly.