Introduction:

Lactic acid bacteria (LAB) are widely used in the food industrial area all over the world. These microbes had got increasing attention since people realized lactic acid bacteria can be used to produce nutritional and pharmaceutical food products (De-Vos and Hugenholtz, 2004). In the dairy industry area, lactic acid bacteria are associated with various fermented food products, for example vegetables, meat, yogurt and whey. Generally speaking, lactic acid bacteria will result in an acidification action in the raw food materials, when they meet the available carbon sources in the raw materials (Kleerebezem and Hugenholtz, 2003). They will format the lactic acid in the raw materials, which is capable of effectively protecting final fermented food products from being sabotaged by microorganisms. However, there are many other uses for lactic acid bacteria metabolism, for instance: enhancing the flavor and texture of products (Kleerebezemab et al., 2000).

Milk and whey are two very important food products in the world, which are rich in protein, carbohydrates, peptides and determined kind of vitamins. The bioactive compounds in them are blessed with the capability of health-promoting. Some of them can help people to defend chronic diseases as well as malnutrition (Korhonen, 2009). Recently, a verity of researches had been done on the bioactive compounds in the food materials associated lactic acid bacteria, large amount of them had been identified and characterized. In this essay, I will focus on the bioactive compounds in the fermentated

milk and whey products, and discuss about the relevant metabolic reactions as well as the effectiveness of their nutritional abilities.

Definition and function of inherent bioactive compounds in milk and whey

Milk and whey are known as a main protein and bioactive compounds supplier among various food products. Many healthy proteins in raw food materials can be enzymatic hydrolyzed or absorbed as well as being used by humans though digesting progress (Korhonen and Pihlanto, 2006). In now days, many advanced technologies served the dairy industry, which will offer great chances for people to isolate, concentrate and modify the bioactive compounds; thus, people could enjoy a healthier live (Michaelidou and Steijns, 2006). For example, lactoferrin (LF) is one typical products of this high technology application. The concentration of LF is quite low in milk and whey, but it is capable of helping people to treat gastrointestinal illness. However, other compounds in different categories are also can have healthy-enhancement functions to peoples bodies, namely: vitamins and nucleotides. Therefore, the definition of bioactive compounds should contain a verity of different categories compounds. According to (Korhonen and Pihlanto, 2006), his definition on the bioactive peptides, in my opinion, bioactive compounds can be defined as special fragments which could have healthy-enhancement or positive effects on human bodies conditions.

The function of bioactive compounds

There are countless bioactive compounds in the milk and whey; generally, those compounds can affect the essential body functional systems like immune systems, gastrointestinal system, cardiovascular systems and nervous systems. The function of those compounds depends on the structure and reaction environment (Korhonen and Pihlanto, 2006). The bioactive compounds can be divided into two types, one is bioactive major compounds, which is bioactive peptides; the other is the bioactive minor compounds, including: growth factors, cytokines, homones, vitamins and nucleotides. For the bioactive peptides, they are major source of energy and amino acid, which are the fuel and important compounds for body growth and maintenance of functional systems. (1) Function of bioactive peptides in the digesting system The bioactive peptides act as essential functional parts during the digesting progress, before amino acids were hydrolyzed and subsequent absorption. Mellander suggested casein-derived phosphorylated peptides, caseinophosphopeptides (CPPs), can positively influence the vitamin-D synthesis, in order to enhanced calcium absorption in the gastrointestinal system. Because CPPs are capable of binding some determining minerals in the digesting area, they have the function of defending people from digesting systems related diseases like osteoporosis, anemia, dental caries and hypertension (Mellander, 1950, Korhonen and Pihlanto, 2006). In addition, some report indicate that CPPs also can enhance mucosal immunity, because of during the synthesis

progress of CPP, IgA level in the intestinal area was increased (Otani, 2000).

(2) Function of bioactive peptides in the nervous system There are peptides with opioid activity exisiting in various casein fractions and can be hydrolyzed using digestive enzymes. Opioid receptors can be found in many places in the body, namely: nervous, immune systems and the gastrointestinal tract of mammals. These opioid peptides can either reduce transit time through affecting smooth muscles in the gut or the transport ability of electrolytes, which leads to change in gastrointestinal function. (3) Function of bioactive peptides in the cardiovascular system The function of peptides in rennin- angiotensin system had been studied for years; the well known one is the angiotensin I-converting enzyme (AEC). It adjusted blood pressure in the body. If the synthesis progress of this kind of peptides occurred in the body system, it will result in antihypertensive effect. (4) Function of bioactive peptides in the immune system According to (Gill, 2000), most whey proteins and proteins as well as peptides isolated from milk are capable of enhancing immune functions through many ways; for instance: antibody synthesis, lymphocyte proliferation and cytokine regulation.

Fig Physiological functionality of milk-derived bioactive peptides (Korhonen and Pihlanto, 2006).

For bioactive minor compounds, it covered a range of chemical compounds. In this chapter, I only list and discussed five of them; namely: growth factors, hormones, cytokines, nucleotides and vitamins.

Fig.

Bioactive minor components in milk (Michaelidou and Steijns, 2006)

In the report of (Michaelidou and Steijns, 2006), he described growth factors are belong to one part of peptides. The mechanism of growth factors and cytokines are almost same, they attached to the determined specific receptors, and delivered messages to the intracellular message receiver, and then lead to the cell proliferation (Michaelidou and Steijns, 2006). In the aspect of vitamin, they are very essential chemical compounds of defending diseases like vascular, neurological and cancer. In other reports, folate can play an important role against infant birth defects. Long-term studies on nucleotides discovered that nucleotides are helpful to enhance the digest system of preterm and small age babies (Michaelidou and Steijns, 2006).

Bioactive compounds from lactic acid bacteria (LAB)

Some species of Lactic acid bacteria can benefit people in aspects of health or nutritional. In the report of (Gilliland, 1990), There are four main ways: enhanced nutritional value of food products, antibiotic actions in intestines, improve the ability of digest system, enhance the ability of anti-carcinogens, controlling serum cholesterol levels in body. Now days, lactic acid bacteria are widely used in the fermentation food industry, which main food product is yogurt. In this review, I will list the main bioactive compounds from the lactic acid bacteria, which are benefit to our bodies. The consequence will follow their four main functions, which had talked above. (1) Process for enhancing food value During the fermentation of the milk and whey, the lactic acid bacteria (LAB) would

generally utilize some vitamins for reproducing. Nevertheless, in the certain cultures like yogurt fermentation, B vitamins like folic acid will be increased. Past reports showed that B vitamins played a very important role in maintaining healthy condition of human body, for example: supporting cell metabolism. Beside B-vitamins, levels of lysine, methionine and tryptophan are also increased in the fermentation progress (Gilliland, 1990). (2) Process for antibiotic actions in intestines The ability of lactic acid bacteria in controlling intestinal pathogens had been studied. In vivo, LAB can also adopt antagonistic actions to some pathogens; for example: bacteriocins are produced by lactobacilli. Bacteriocins are capable of inhibiting the growth of organisms, which close related to them (Gilliland, 1990). (3) Process for improving lactose utilization The enzyme -galactosidase is the typical bioactive product of LAB fermentation process, which is a great help to those lactose maldigestors. This is because the function of enzyme -galactosidase is improving lactose utilization in the bodies of consumers.

The

functionality

of

antimicroal

peptides

and

immunomodulating peptides
The functionality of immunomodulating peptides Milk and whey are capable of providing a number of important nutrients to people. Most of these nutrients are proteins. Some proteins may contain immunomodulating

peptides, which can theoretically affect immunological reactions and cellular functions after being released in the gut. These peptides are either naturally existed in the whey or being synthesized by enzymatic hydrolysis through the immune responses. In fact, most immunomodulating peptides functionality are evaluated by the ability of influencing determined immune system through affecting antibody Production and cytokine secretion lymphocyte activation and proliferation. Examples of immunomodulating peptides in the whey protein concentrates (WPCs) and whey protein isolates (WPIs) are commonly lactoferricin (LFc), beta-lactoglobulin (-LG) and alpha-lactalbumin (-LA) (Gauthier et al., 2006). In the fig, it illustrates various peptides in the whey protein isolates and whey protein concentrates had different effect on lymphocyte proliferation. For those immunomodulating peptides (LFc, -LG, -LA), they stimulated the lymphocyte proliferation, in order to enhance the immune system.

Fig.

Effects of whey protein products (

inhibiting,

stimulating, # no effect),

purified whey proteins, enzymatic hydrolysates (H) and peptides on lymphocyte proliferation (Gauthier et al., 2006).

The functionality of antimicrobial peptides

Antimicrobial peptides (AMPs) are normally amphiphilic and cationic compounds, which are usually bacteria-killing. They use the similar way to kill bacteria, which is using positive charge interacted with negative charge permeabilizing the cell membranes of bacteria. To animals, antimicrobial peptides are playing an essential role in the body immunity that is very important in early defense against invading microorganisms. To the aspect of bacteria, antimicrobial peptides synthesized by bacteria are bacteriocins. The bacteriocins are divided into two types: one is produced by Gram-negative bacteria; the other is produced by Gram-positive bacteria. For the first type, they are usually proteins larger than 20kDa, which only preventing closely related strains from growing. In contrast, the peptide bacteriocins produced by Gram-positive bacteria are usually smaller than 6 kDa. They are usually membranepermeabilizing peptides, cationic and amphiphilic. However, these peptide bacteriocins are showing a higher specific activity, when compared to the first type. The metabolic pathway of antimicrobials (nisin) Nisin is one typical antimicrobial, which had large molecular weight of 7000. It was synthesized by streptococcus lactis and was consist of two submits (Ingram, 1969). Generally, nisin could be synthesized under condition that S~reptococcus lactis strain 354/07 (NCDO 497) cells are incubated in a buffered salts solution containing, amino

acids, vitamins, pyrimidine bases and purine glucose. Ingram (1969) reported that it contained two unique sulphur-containing amino acides, namely: lanthionine and -methyldehyfroalanine; nisin also had two , unsaturated amino acids: dehydroalanine and -methyldehydroalanine. In the experiment, serine, cysteine and threonine are precursors of -methyldehyfroalanine and lanthionine. Thus, one mechanism of nisin synthesis could be indicated in the following fig.

Fig proposed pathway for synthesis of lanthionine and -methyldehyfroalanine (Ingram, 1969) Therefore, the two unique sulphur-containing amino acids of nisin could be produced from cysteine plus serine and threonine. However, very sensitive to chloramphenicol. . Table: the effects of antibiotics on lanthionine peptide synthesis the figures in parentheses represent the incorporation of cysteine into hot trichloroacetic acid-precipitable material. IOO % synthesis of lanthionine peptide corresponded to 1738 counts/min (Ingram, 1970).
bioassay indicated that

this progress is

In the report of (Ingram, 1970),t incorporation of radioactive amino acids was used to propose a mechanism of synthesis of the lanthionine residues. In the table, chloramphenicol, chlortetracycline and puromycin syntheses the peptide inhibited lanthionine, which is a ribosomal mechanism (Ingram, 1970)The amino acid cysteine in the process is a precursor of the lanthionine and -methyldehyfroalanine residues of nisin. Thus, in order to increase the concentration of nisin, chloramphenicol should be avoid in the process (Ingram, 1969, Ingram, 1970). However, there are many other physical and chemical methods to increase the concentration of nisin, like: changing reaction temperature, modulating PH.

Lactic acid bacteria is consist of two parts, one is rods (bifidobacterium, lactobacillus); the other one is cocci (pediococcus, streptococcus, leuconostoc). Their pathways of carbohydrate fermentation vary from each other, but their final products are similar: either completely or more than 50% lactate (Kandler, 1983).

Table the genera of lactic acid bacteria, their fermentation type and products (Kandler, 1983) Effectiveness of bioactive compounds in milk in improving health Milk products are capable of developing and maintaining a healthy body condition in all mammals. However, milk of different species contain different levels and kinds of bioactive compounds, for instance percentage protein of rabbit is 14 times bigger than that of human. In the food industry, people focus on the protein portion in the milk, which is one of the major components responsible of nutrition value of milk (Zinn, 1997). For infant, there is potential hazard in terms of consuming artificial neonates fed colostrums may lead to degradation in immune system and enteric disorder. According to Zinn (1997), infants who are breast-fed for over 6 months have fewer health diseases in the future lives than their counterparts who are formula-fed. In the aspect of proteins in the milk, hormones proteins from hypothalamus (somatotropin-releasing hormone and somatostain), anterior pituitary gland (prolactin and somatortopin) and gut( vasoactive intestinal peptide, substance P and gastrin) (Zinn, 1997). Besides proteins, various growth factors as well as a large number of bioactive

peptides, namely: epidermal growth factor (EGF), lactoferrin transferring, insulin-like growth factor (IGF) I and II, IGF binding proteins (Zinn, 1997) .

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