Kallidin and bradykinin are naturally generated bioactive peptides in body fluids and tissues through proteolytic cleavage, and they function as vasodilators for the maintenance of normal blood pressure Wu a ; Lafarga and Hayes Like arginine-vasopressin in other mammals , lysine-vasopressin in pigs is a peptide hormone that stimulates the reabsorption of water in the distal tubules of the kidney, leading to the formation of more concentrated urine Nielsen et al. For protein and peptide syntheses in an animal body, a pool of free AAs must be available simultaneously at the site of the syntheses.
Free AAs normally result from the catabolism of dietary and body proteins. Failure to obtain enough AAs from diets will result in intense degradation of body proteins, especially the muscle proteins, because muscle is the largest, dynamic, body protein reservoir. As other dietary AAs, the small intestinal absorption of free lysine is generally more rapid than the absorption of protein-bound lysine, and the rates of absorption of protein-bound AAs have been shown to vary and may be affected by the source of protein, its degree of processing, as well as the energy component of the diet Leibholz et al.
From a human study Uhe et al. Compared to other essential AAs, free lysine is more concentrated in the intracellular space of muscle tissue, which suggested that muscle serves as a body reservoir for free lysine. Besides its primary function as a building block for biosynthesis of proteins and peptides, lysine also functions as a substrate for generation of numerous non-peptide molecules, which include low molecular-weight nitrogenous substances e.
Each of these metabolites has specific biochemical and physiological importance for animal life processes. Besides a role in normalizing blood cholesterol and triglyceride concentrations, carnitine plays additional physiological roles in protecting organisms from oxidative stress, promoting substrate oxidation in brown adipose tissue, improving cardiac performance, and regulating energy partitioning in the body Ferrari et al.
Hydroxylysine is synthesized from lysine by lysyl hydroxylase reaction called hydroxylation Hausmann As is known, collagen is the most abundant family of proteins in the extracellular matrix of connective tissues which include skin, bone, cartilage, and tendon, while elastin is another major component of certain soft connective tissues, such as arterial walls and ligaments Halper and Kjaer Both collagen and elastin are cross linked to form fibrous proteins based on aldehyde formation from the amine side chains of lysine or hydroxylysine residues, and it is lysyl oxidase, an enzyme, that converts the amine side chains of the lysine or hydroxylysine residues into aldehydes Eyre et al.
In addition, hydroxylysine also represents special sites for the attachment of carbohydrates in collagen Gelse et al. Both collagen and elastin play very important roles for defining the structural integrity and physiological functions of the extracellular matrix of connective and muscle tissues Purslow et al. Glutamate is the most significant excitatory neurotransmitter in the mammalian central nervous system, and lysine, present at high concentration in the brain, is an important precursor for de novo synthesis of glutamate.
Papes et al. Cadaverine is a foul-smelling diamine compound a type of polyamine with exactly two amino groups produced by protein hydrolysis during putrefaction of animal tissue, and specifically it is synthesized from lysine in a one-step reaction with lysine decarboxylase Andersson and Henningsson Although polyamines in general are recognized as cell growth factors in relation to cell proliferation, differentiation, regeneration, and malignant transformation, the specific physiological functions of cadaverine are not clear Patocka and Kuehn Like carbohydrates and lipids, AAs can also be used to meet animal energy requirement, especially when carbohydrates and lipids become unavailable to provide enough energy for animals.
The glucogenic AAs can also provide energy through gluconeogenesis pathway. Secondly, as aforementioned, there is a constant protein turnover in virtually all living cells, and based on its own AA composition each protein requires a certain ratio of free AAs supplied for its synthesis.
Molecular Mechanisms of Protein Biosynthesis
At a given time, the cellular free AA ratio usually does not exactly match the cellular requirements for syntheses of new proteins and, furthermore, most cells or tissues unfortunately do not have a mechanism to store free AAs. Thirdly, during starvation or in uncontrolled diabetes mellitus, when carbohydrates are either unavailable or not properly utilized, cellular proteins, especially those from muscle tissue, will be utilized as fuel for the body.
AAs are an important and specifically required fuel for several tissues.
During feeding, the splanchnic bed extracts and immediately oxidizes a large amount of enteral non-essential AAs, including the totality of glutamate and the majority of glutamine and alanine Battezzati and Riso Stoll et al. During exercise, muscle AAs may produce significant amounts of energy via deamination of aspartate to provide ammonia for the synthesis of adenosine monophosphate AMP from inosine monophosphate IMP and intermediates for the TCA cycle Battezzati and Riso After absorption, the free lysine in excess of the needs for syntheses of proteins and other substances will be catabolized in a cell- and tissue-specific manner Gatrell et al.
The intestinal oxidation of enteral lysine contributed one-third of total body lysine oxidation in growing pigs fed a high-protein diet van Goudoever et al. Other tissues such as liver, kidney, muscle, and brain also contribute to the whole body lysine catabolism.
A general formula of lysine. Presented in this formula is an ionized form of lysine. These two pathways differ in that the saccharopine pathway is predominantly mitochondrial, whereas the pipecolate pathway is predominantly peroxisomal and cytosolic Hallen et al. Lysine catabolism in monogastric animals.
Lysine is catabolized via the saccharopine pathway and the pipecolate pathway. Adapted from Wu a. The primary pathway of lysine catabolism is thought to be the saccharopine pathway in liver Papes et al. Small portion of lysine are catabolized in the brain through pipecolate pathway Chang The ability of mammalian brain to synthesize pipecolic acid suggests a role as a neurotransmitter, and in pathological situations pipecolic acid accumulates in body fluid Broquist In addition to the two pathways just discussed, there are some other undefined pathways that can also contribute to lysine catabolism, which include those depending on lysyl oxidase, L-AA oxidase, and carnitine biosynthesis Benevenga and Blemings ; Gatrell et al.
While the amino groups of lysine are converted to ammonia, which is further converted to urea or uric acid through the urea cycle, the end product of the carbon skeleton catabolism is acetyl-CoA, which is further catabolized for energy via TCA cycle or converted to ketone bodies or fatty acids. Because acetyl-CoA is the fuel for the TCA cycle and cannot be converted to glucose by pigs and other mammals, lysine is strictly ketogenic in nature.
The carbon atoms in ketone bodies are ultimately degraded to carbon dioxide via the TCA cycle to produce energy for the animal body Berg et al. Nonetheless, of all essential AAs, lysine is the most strongly conserved one, as demonstrated in rats and chicks Flodin ; Benevenga and Blemings Meredith et al. These findings suggested that lysine is unique in that it is less catabolized than most, if not all, other essential AAs. This unique conservative nature of lysine is very interesting because lysine is the most deficient AA in almost all typical diets for monogastric animals such as pigs.
Beyond the metabolic functions described above, lysine also exerts many physiological functions for monogastric animals.
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Lysine can affect animal metabolism of other nutrients, hormone production, and immunity Wu a ; Wu b. More remarkably, peptide bound lysine is a potential active site of post-translational modification PTM and epigenetic regulation of gene expression.
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Understanding these physiological functions of lysine within the animal body is requisite for animal scientists and producers to better use lysine for promoting animal health and production Wu a. AAs are directly and indirectly related to each other within the overall nutrient metabolism pathways, and the plasma AA concentrations reflect the whole sum of the metabolic flow from all organs and tissues Yen et al.
Interactions among AAs within an animal body alter the expected release of AAs into the blood from diet.multiphp-nginx.prometdev.com
Biologists discovered a new facet of the mechanism of protein biosynthesis
Lysine-arginine antagonism is one of the classic examples of the interactions. Another example of AA interactions is the interaction among three branched-chain AAs leucine, isoleucine and valine. Garcia-Villalobos et al. They assumed that typical diets formulated to meet the requirement of lysine contain excess of leucine, which may depress the absorption of lysine causing depression of pig performance.
Their results indicated that the dietary leucine to lysine ratio affects the expression of cationic AA transporters in jejunum and muscle, and therefore, affects plasma AA profile. A study of plasma AA network structure in rats showed that a single AA deficiency can affect plasma AA profiles, for which lysine is located at the top control level, affects the metabolism of almost all other AAs, but is not influenced by others Shikata et al. Zimmerman and Scott reported that dietary lysine deficiency resulted in increased plasma concentrations of some AAs, notably isoleucine, threonine and valine in chicks.
Braude et al. They found that the concentration of lysine in blood plasma increased linearly over a wide range of lysine content, but the concentrations of most other AAs, however, were largely unaffected. Similarly, Roy et al. The plasma concentration of histidine decreased, and the concentration of serine increased in pigs fed either lysine deficient or excess diet.
The plasma concentrations of all other AAs were not affected by the diets. Besides on other AAs, dietary amount of lysine also has effects on the metabolism of other nutrients.
Jarowski and Pytelewski supplemented a control diet with 0. Dietary lysine supplementation can regulate Ca metabolism, specifically enhancing intestinal Ca absorption and improving renal conservation of the absorbed Ca Civitelli et al. With lipopolysaccharide-treated neonatal pigs, Carter et al. In addition, lysine can form transitory complexes in various enzymes with cofactors including biotin, pyridoxal, and lipoate Broquist With human liver tissue, Zhao et al.
It has been recognized that insulin, growth hormone GH , glucocorticoids, insulin-like growth factor 1 IGF-1 , thyroid hormones, and some other hormones regulate body protein and energy metabolism including muscle protein turnover Breier ; Liu et al. Among these hormones, GH, IGF-1, and their associated carrier proteins and receptors work together as a multi-level hormonal system called the somatotropic axis Breier ; Tomas et al. Previous research in rats showed that the activity and function of this axis can be significantly affected by the nutritional status, such as plasma AA levels or dietary AA supply Straus and Takemoto ; Takenaka et al.
In nursery pigs fed a low-lysine diet 0. In other studies with growing pigs, however, dietary lysine did not show influence on plasma GH and IGF-1 concentrations Roy et al. Different lysine levels and different animal physiological status may explain the discrepancy of the aforementioned studies. Due to the lysine-arginine antagonism, administration of these two AAs together may have some antagonism elimination effect.
It was reported that oral administration of a combination of lysine 1. In primiparous sows, high lysine intake increased postprandial concentrations of insulin and IGF-1, in which the effect was from a combination of lysine and other AAs Yang et al. Insulin is secreted primarily in response to the elevated blood concentration of glucose. Other nutrient stimuli including AAs can also promote insulin secretion.
Although there are large differences among AAs in their capacities to stimulate insulin secretion, intravenous administration of lysine significantly increased the plasma insulin level in adult human subjects Floyd et al. Some recent studies also suggested that lysine has a stimulating effect on insulin secretion, but this effect may be in a dose dependent manner. Roy et al. Similarly, Ren et al. However, when the lysine level was further increased to 1.
The interactions between lysine and the aforementioned hormones might lead to a modification of either translational or transcriptional, or both events of protein synthesis in pigs Ren et al.
The Genetic Code
Surprisingly, how dietary lysine at different levels affect the activities of insulin and somatotropic axis pathway has not been thoroughly studied. Epigenetics is defined as the study of heritable changes in gene activity and expression that occur without alteration in DNA sequence, and it is known that these heritable changes are tightly regulated by two major molecular modifications, DNA methylation and histone modifications, amongst several others Goldberg et al.
While DNA methylation refers to the addition of a methyl group to the cytosine or adenine nucleotides of DNA, histone modifications mean the chemical modifications of histone proteins.