Where to find the problem 4 – Free amino acids

The effects of lysine

as a food additive have been studied by the Food and Nutrition Science Programme of the Department of Biochemistry at Carleton University in Canada and the Canadian Food Inspection Agency and its Bureau of Nutrition Science.

L-lysine is a popular food additive, but the physiological effects of excessive L-lysine supplementation are poorly understood and there is no upper limit for safe intake.

This study aimed to investigate the effects of increased L-lysine intake on body weight, feed intake and various haematological and biochemical blood parameters.
Lysine supplementation of more than 1.5 % of the protein content influenced the parameters investigated (Chao-Wu Xiao, Carla Wood, Jesse Bertinato, 2019).

Glyphosate damages the microbiome of animals due to glyphosate residues in GM soya
In a eubiotic gut flora, the beneficial gut bacteria produce 1 mg nicotinic acid from 60 mg tryptophan. Humans also synthesise nicotinic acid (vitamin B3) from tryptophan in the liver.

The conversion of tryptophan to nicotinic acid in the liver is known as the kynurenine pathway.
The first step in the kynurenine pathway is carried out by the enzyme indoleamine-2,3-dioxygenase (IDO). This enzyme is known as the rate-limiting enzyme as it determines the availability of NAD+ (the end product of the kynurenine pathway). The liver plays a crucial role in the function of tryptophan nicotinamide metabolism. The function of the IDO enzyme depends on nitric oxide. The IDO enzyme is an essential component of the immune system and plays a role in the natural defence against various pathogens.
The availability of the amino acid tryptophan plays a key role in the modulation of T cell activity.
T cells react sensitively to a lack of tryptophan. An essential amino acid in its microenvironment confers strong immunomodulatory properties to the active IDO in the expressing cell (Laura Vallius, 2011).

What could impair the function of the IDO enzyme?

The function of the IDO enzyme depends on nitric oxide (NO). An NO deficit exists due to a local arginine deficiency and lysine-arginine antagonism. NO limits the availability of tryptophan-nicotinamide conversion in the “de novo” kynurenine pathway.
Healthy mitochondrial function is only possible if the kynurenine pathway functions normally. It influences various biochemical processes:

– Cholesterol metabolism
– Oestrogen and testosterone synthesis
– Neurotransmitter metabolism
– Production of free radicals
– Detoxification

Nicotinic acid is amidated in the liver. The only precursor of NAD+ is nicotinamide. Nicotinamide is found in all body cells, not just liver cells.
Glyphosate residues damage the cytochrome p450 enzyme system of the liver. It inhibits the enzyme adenylyltransferase, which is responsible for the conversion of nicotinic acid into nicotinamide.
Amidated nicotinamide is found in all body cells, not just liver cells. Studies have shown that the liver plays a crucial role in tryptophan-nicotinamide metabolism.

The Szent-Györgyi cycle, or citrate cycle, is an essential metabolic process in all living cells that use oxygen for cellular respiration. The energy released during the oxidative steps of the process is transferred to NAD+ in the form of high-energy electrons. The result is NADH.

In the citrate cycle, three NADH molecules are formed together with the electron acceptor FAD to form FADH2.

Almost 90 % of the energy consumed with food is generated in the citrate cycle by the conversion of NAD+ → NADH via electron transport. NAD+ is converted into the reduced form NADH by accepting a hydrogen atom and two electrons.

If NAD+ production is disrupted, the citrate cycle is also disrupted and mitochondrial energy production decreases. A lack of NAD+ impairs cell function, cell protection and energy production and is a key pathological factor in many diseases and in the ageing process. Sufficient production of NAD+ is a prerequisite for the healthy functioning of the body.