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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Cereal Storage Protein Description
  5. Cereal Health Benefits
  6. Cereal Grain Protein Health Benefits
  7. Predicted Biological Activity of Cereal Grain Peptides
  8. Concluding Remarks
  9. References

 Cereal grains, such as wheat, barley, rice, rye, oat, millet, sorghum, and corn, have been staples in human diets since ancient times. At present, there is a significant body of scientific evidence showing the health benefits of consuming whole grains in chronic disease prevention, particularly in regards to diabetes, cardiovascular disease, and cancer. The objective was to determine bioactive peptides in cereal grains that may prevent cardiovascular disease, cancer, inflammation, and diabetes. Bioactive peptides that may be obtained from cereal grains, particularly wheat, oat, barley, and rice, were identified. Bioactive peptides that play a role in chronic disease prevention have been found primarily in legumes and dairy products; although research connecting cereal grains with potential bioactive peptide activity is limited. In this review, 4 cereal grains, wheat, oat, barley, and rice, were evaluated for bioactive peptide potential using the BIOPEP database. In addition, research information was compiled for each grain regarding evidence about the effect of their proteins in prevention of chronic diseases. All 4 grains showed high occurrence frequencies of angiotensin-converting enzyme-inhibitor peptides (A = 0.239 to 0.511), as well as of dipeptidyl peptidase-inhibitor and antithrombotic, antioxidant, hypotensive, and opioid activity. Wheat and rice proteins had anticancer sequences present. Wheat and barley showed the greatest diversity and abundance of potential biological activity among the cereal proteins. Further research needs to be conducted to learn how these biologically active peptide sequences are released from cereal grains. This study supports the notion that cereal grains are a nutritious part of a healthy diet by preventing chronic diseases.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Cereal Storage Protein Description
  5. Cereal Health Benefits
  6. Cereal Grain Protein Health Benefits
  7. Predicted Biological Activity of Cereal Grain Peptides
  8. Concluding Remarks
  9. References

Cereal grains have been a staple in human diets around the world since ancient times. They have been consumed as a major source of energy for billions of people, as well as contributed to the majority of livestock feed. Cereals have been cultivated in many regions in the world and are prevalent in some form in all diets, from a Western diet based on wheat to an Asian diet based on rice. Cereal production is a large global industry that produces food, animal feed, consumer goods, and ingredients. There are many different types of cereals, but some of the most common include wheat (Triticum aestivum), barley (Hordeum vulgare), rice (Oryza sativa), and oat (Avena sativa), with wheat and rice being 2 of the 3 most important food crops that contribute to more than half of all calories consumed by humans (Awika 2011).

Cereals are classified as belonging to the Gramineae (Grasses) family and include rice, ragi, tef, millets, maize, sorghum, wheat, barley, rye, and oats (Figure 1; Cunsolo and others 2012). Classification of the grains within this family depends on protein structure, which can contribute largely to the nutritional and functional properties of the cereal. Protein content in cereal grains range from 10% to 15% of the dry grain, with the greatest share, almost one-half, coming from storage proteins (Shewry and Halford 2002). Figure 2 shows major storage proteins in grains, such as prolamins, germins, and globulins (Cunsolo and others 2012). Prolamins are the major storage proteins in most cereals, with the exception of rice and oat, which are higher in globulins. Wheat and barley (Triticeae tribe) prolamins are related proteins to oat (Aveneae tribe), while rice (Bambusoideae tribe) is more distantly related (Cunsolo and others 2012). Dietary proteins, from food sources other than cereals, have long been studied to identify bioactive peptides within, which have been shown to have various health benefits, including prevention against cancer, diabetes, inflammation, obesity, and cardiovascular disease (Udenigwe and Aluko 2012). Cereal grains, though high in carbohydrates, also contain a substantial amount of protein, thus their potential to provide bioactive peptides in the diet.

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Figure 1. Taxonomic tree of Graminae. Adapted from Cunsolo and others (2012).

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Figure 2. Classification of wheat proteins and their structural relationships. Adapted from Cunsolo and others (2012).

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Obesity and heart disease are growing epidemics in the world, with obesity now being the leading preventable cause of death in the United States (Liu and Elmquist 2012). This only further upholds the idea that maintaining a healthy lifestyle is imperative. For years it has been shown that a diet rich in whole grains, protein, and unsaturated fats, like the Mediterranean diet or the Asian diet, leads to good weight management and a lower risk of chronic diseases (Vincent-Baudry and others 2005; Dixit and others 2011). Most of these diets include regular consumption of cereal grains, with wheat being a significant source within the Mediterranean diet.

The Mediterranean diet consists of using culinary techniques, foods, and flavor profiles of the Mediterranean area, which include “healthy fats,” whole grains, vegetables, fresh fish, occasional red wine consumption, herbs, and spices. This type of diet limits the use of salt, and “unhealthy fats,” and focuses on using cereal grains and vegetables as the foundation of the meal rather than meat. Many studies have shown the health benefits of this diet; specifically focusing on how it reduces inflammation and risk factors of cardiovascular disease (Estruch and others 2006; Camargo and others 2012). What is not as clear is which dietary factors contribute most to the reported health benefits.

Cereal grains have been shown to have many functional and bioactive properties from their high fiber content to their antioxidant activity, but the effects of their proteins are often overlooked (Harris and Kris-Etherton 2010). Based on the bioactive properties that proteins contain in other foods, such as legumes, it is reasonable to believe that cereal proteins have similar properties and functions (Cam and de Mejia 2012).

The objectives of this investigation were to review the available research demonstrating that proteins and peptides in cereal grains, specifically wheat, barley, oat, and rice, have bioactive properties that may help lower markers of cardiovascular disease and inflammation and, in addition, those that may play a role in increasing satiety. Another objective was to present a scientific systematic calculation of the bioactive peptides that may be potentially obtained from wheat, barley, oat, and rice cereal grains.

Cereal Storage Protein Description

  1. Top of page
  2. Abstract
  3. Introduction
  4. Cereal Storage Protein Description
  5. Cereal Health Benefits
  6. Cereal Grain Protein Health Benefits
  7. Predicted Biological Activity of Cereal Grain Peptides
  8. Concluding Remarks
  9. References

The main storage proteins in wheat are prolamins, which include gliadins and glutenins. The storage proteins that are reviewed in Table 1 were found on the BIOPEP protein database and were chosen because they are major storage proteins in wheat. A 30% to 40% of wheat protein is made up of gliadins, mostly alpha, beta, gamma, and omega types. Alpha and beta types are thought to be the proteins that contribute most to gluten intolerance, and together with wheat glutenins, they form gluten protein structures found in bread (Zilic and others 2011). Glutenins are categorized into 2 groups, high-molecular-weight (HMW) and low-molecular-weight (LMW), and are considered large protein molecules based on their quaternary structures (Zilic and others 2011). Together, glutenins and gliadins consist of up to 90% wheat proteins (Zilic and others 2011).

Table 1. Wheat seed storage proteins
Wheat proteinIDSequence*Amino acid residuesMolecular mass
  1. *Amino acid nomenclature: C, cys; cysteine; H, his; histidine; I, ile; isoleucine; M, met; methionine; S, ser; serine; V, val; valine; A, ala; alanine; G, gly; glycine; L, leu; leucine; P, pro; proline; T, thr; threonine; F, phe; phenylalanine; R, arg; arginine; Y, tyr; tyrosine; W, trp; tryptophan; D, asp; aspartic acid; N, asn; asparagine; B, asx; either of D or N; E, glu; glutamic acid; Q, gin; glutamine; Z, glx; either of E or Q; K, lys; lysine; X, undetermined amino acid. Protein sequence was obtained from BIOPEP database.

LMW glutenin1329MKTFLVFALLALAAASAVAQISQQQQPPPFSQQQQPPFSQQQQPPFSQQQQSPFSQQQQQPPFSQQQQPPFSQQPLISQQQQLPFSQQQQPQFSQQQQPPYSQQQQPPYSQQQQPPFSQQQQPPFSQQQQPSFSQQQQQPPFTQQQQPPFSQQSPISQQQQQQQQQQQQPFTQQQQPPFSQQPPISQQQQPPFSQQQQPPFSQQQQIPVIHPSVLQQLNPCKVFLQQQCIPVAMQRCLARSQMLQQSICHVMQRQCCQQLRQIPEQSRHESIRAIIYSIILQQQQQQQQQQQQQQQGQSIIQYQQQPPQQLGQCVSQPQQQLQQQLGQQPQQQQLAHGTFLQPHQIAQLEVMTSIALRTLPRMCSVNVPLYETTTSVPLGVGIGVGVY38833,052.6836
HMW glutenin1342MEGEASEQLQCDRELQELQERELKACQQVMDQQLRDISPECHPVVVSPVAGQYEQQIVVPPKGGTFYPGETTPPQQLQQRIFWGIPALLKRYYPSVTCPQQVSYYPGQASPQRSRDITSSSYHVSVEHQAASLKVAKAQQLAAQLPAMCRLEGGDALSASQ16117,355.4648
Alpha-gliadin1305MKTFLILALVATTATTAVRVPVPQLQPKNPSQQQPQEQVPLVQQQQFPGQQQQFPPQQPYPQPQPFPSQQPYLQLQPFPQPQPFLPQLPYPQPQSFPPQQPYPQQRPKYLQPQQPISQQQAQQQQQQQQQQQQQQQQQILQQILQQQLIPCRDVVLQQHNIAHASSQVLQQSTYQLLQQLCCQQLLQIPEQSRCQAIHNVVHAIIMHQQEQQQQLQQQQQQQLQQQQQQQQQQQQPSSQVSFQQPQQQYPSSQVSFQPSQLNPQAQGSVQPQQLPQFAEIRNLALQTLPAMCNVYIPPHCSTTIAPFGIFGTN31335,525.9180
Gamma-gliadin1317MNIQVDPSSQVPWPQQQPFPQPHQPFSQQPQQTFPQPQQTFPHQPQQQFSQPQQPQQQFIQPQQPFPQQPQQTYPQRPQQPFPQTQQPQQPFPQSQQPQQPFPQPQQQFPQPQQPQQSFPQQQPSLIQQSLQQQLNPCKNFLLQQCKPVSLVSSLWSMILPRSDCQVMRQQCCQQLAQIPQQLQCAAIHSIVHSIIMQQEQQEQRQGVQILVPLSQQQQVGQGTLVQGQGIIQPQQPAQLEVIRSLVLQTLATMCNVYVPPYCSTIRAPFASIVAGIGGQYR28231,502.6309
Omega-gliadin1418MKTFLIFVLLAMAMKIATAARELNPSNKELQSPQQSFSYQQQPFPQQPYPQQPYPSQQPYPSQQPFPTPQQQFPEQSQQPFTQPQQPTPIQPQQPFPQQPQQPQQPFPQPQQPFPWQPQQPFPQTQQSFPLQPQQPFPQQPQQPFPQPQLPFPQQSEQIIPQQLQQPFPLQPQQPFPQQPQQPFPQPQQPIPVQPQQSFPQQSQQSQQPFAQPQQLFPELQQPIPQQPQQPFPLQPQQPFPQQPQQPFPQQPQQSFPQQPQQPYPQQQPYGSSLTSIGGQ28032,553.4199

Oat, like wheat, is also part of the Gramineae family, though it differs in tribe (Aveneae) compared to wheat and barley (Triticeae; Cunsolo and others 2012). Unlike wheat, the major storage proteins in oats are globulins, known as avenalins, which are a part of the cupin, rather than prolamin, protein superfamily (Cunsolo and others 2012). Avenalins can make up almost 80% of the oat protein, whereas the other common storage protein, the prolamin avenin, makes up only about 15% of the total proteins found in oat (Klose and others 2009). On average, oat contains about 13% total protein (Sadiq Butt and others 2008). Some of the main storage proteins in oat include 11S globulin, 12S globulin, and avenin. Compared to most cereal grains, oat contains a significant amount of high-quality protein and amino acids (comparable to soy and meat protein quality), though it is still an incomplete protein due to its lack of lysine (Biel and others 2009). Oat lacks the protein matrix characteristic of wheat that presents storage proteins insoluble in salt solutions; however, in oat, a large portion of these proteins are saltwater-soluble globulins. Most of the metabolically active proteins in oat are in the water-soluble albumin fraction (1% to 12%). Oat protein distribution affects the amino acid composition with high lysine content, compared to other cereals, and relatively lower glutamic acid and proline content. The peptides produced after digestion of oat can be tolerated by people with gluten intolerance or allergies (Klose and others 2009).

Barley and wheat are the 2 most closely related cereal grains in the Gramineae family, both belonging to the Triticeae tribe (Cunsolo and others 2012). Like wheat, the main storage proteins in barley are prolamins, specifically hordeins. In a typical barley grain there is about 10% to 17% protein content, though this range decreases when the barley is dehulled (Baik and Ullrich 2008). Barley protein is relatively nutritious, though it is not often utilized as a protein source in modern diets. The storage proteins that are reviewed here include B hordein, C hordein, D hordein, and globulin. Though barley is not as well researched as wheat, there is much interest in the proteins of barley, their functions, and how these proteins can influence crop quality (Østergaard and others 2004).

Rice storage proteins have comparable nutritional quality to oat storage proteins and include albumins, glutelins, globulins, and prolamin fractions (Cao and others 2009). Rice glutelins are the most prevalent storage proteins, making up as much as 75% of the grain protein content. Prolamins, though common in the other grains mentioned above, account for only 5% of rice proteins (Krishnan and Okita 1986). Like oat, rice protein is hypoallergenic and thus does not contribute to intolerances or allergic reactions in people with celiac disease or gluten intolerance. The rice storage proteins evaluated in this review are 2 different prolamin fractions and glutelin found on the BIOPEP protein database. Rice does not normally contain high amounts of protein, but research has been conducted to prepare rice protein isolates from rice flours using different techniques, such as carbohydrate-hydrolyzing enzyme treatment with α-amylase, glucoamylase, cellulase, and xylanase to yield a product with 91% protein (Shih and Daigle 2000).

Cereal Health Benefits

  1. Top of page
  2. Abstract
  3. Introduction
  4. Cereal Storage Protein Description
  5. Cereal Health Benefits
  6. Cereal Grain Protein Health Benefits
  7. Predicted Biological Activity of Cereal Grain Peptides
  8. Concluding Remarks
  9. References

A number of studies have shown that cereal grain consumption can lower markers of chronic disease. A study done with lean and obese Zucker rats showed that wheat bran consumption lowered plasminogen activator inhibitor-1 levels in the obese rats to the levels observed in the lean rats (Belobrajdic and others 2011). This was partially attributed to antioxidant capacity and the ability for wheat bran to modestly reduce oxidative stress. Several studies also confirmed the antioxidant effects found in various wheat varieties (Benedetti and others 2012). One human trial involved feeding the participants a controlled whole grain diet to observe which health markers changed between the control and experimental groups (Giacco and others 2010). The results showed a decrease in fasting cholesterol and low-density lipoprotein (LDL) cholesterol levels. A wheat-based, specially processed cereal was fed to rats that showed an increase in antisecretory factor, which is known to prevent inflammation and pathologic fluid secretion (Johansson and others 2011). Oat bran fed to LDL-receptor-deficient mice has been shown to reduce atherogenesis, though the exact components of the oat bran responsible for the effects were unknown (Andersson and others 2010). Oat also showed to have anti-inflammatory, antioxidant, cholesterol-lowering, anticancer, immunomodulating, satiety, and antidiabetic effects in many in vivo and in vitro studies (Singh and others 2013).

Barley has been shown to contain several bioavailable and bioactive peptides, including lunasin, angiotensin-converting enzyme (ACE)-inhibitory peptides, and xanthan oxidase-inhibitory peptides (Jeong and others 2010; Lee and others 2010). Another study that utilized germinated barley demonstrated how this protein- and fiber-rich prebiotic reduced inflammation in mice with induced chronic colitis, which could lead to new treatment options for irritable bowel disease (Kanauchi and others 2008). Postprandial glucose levels were lowered in diabetic patients who consumed Prowash barley, a type of hull-less barley that is high in fiber and protein (Rendell and others 2005). These results were similar to the levels seen in diabetic patients with alpha-glucosidase treatment, which favors barley as a food for people in a prediabetic state. Rice is known to contain phytic acid in the bran portion of the grain, which, along with the bran, has been shown to inhibit cancer cell growth (Norhaizan and others 2011), as well as to reduce the risk for hypoglycemia in mice caused by a high-fat diet (Kim and others 2010).

Less commonly consumed grains in the United States, such as rye, also have many reported health benefits. A study looked at the difference between rye and wheat bread linked with lower insulin response and found that rye consumption produced different metabolites during digestion and resulted in higher satiety and possibly a beneficial reduced inflammatory response (Bondia-Pons and others 2011). Another study compared the prostate-specific antigen (PSA) concentrations of men with prostate cancer who either consumed rye whole grain and bran or a refined wheat diet with added cellulose (Landberg and others 2010). Results showed significantly lower plasma PSA and fasting plasma insulin levels in the rye whole grain group, suggesting rye's ability to inhibit prostate cancer progression due to a decreased exposure of the group to insulin. Alkylresorcinols, bioactive phenolic lipids found in whole grains, were isolated from rye bran and could be a reason for whole grain lowering the risk of type-2 diabetes due to reported decreases in plasma levels of free fatty acids from reduced lipolysis (Andersson and others 2011).

Amaranth is another important grain growing in popularity in the United States. In a 2009 study comparing amaranth, a pseudocereal, with cereal grains, amaranth had a stronger radical-scavenging ability (22.6 mg gallic acid equivalent/g) against 1,1-diphenyl-2-picrylhydrazyl radicals than other cereals (2.5 to 17.7 mg gallic acid equivalent/g; Asao and Watanabe 2010). From a large number of human and animal studies, amaranth has been shown to be high in protein, fiber, vitamins, and antioxidant activity, antianemic activity, antitumor effect, and anti-hypertensive effect (Caselato-Sousa and Amaya-Farfán 2012). Amaranth has also been shown to modulate serum cholesterol levels in human and animal trials (Caselato-Sousa and Amaya-Farfán 2012).

Overall, cereal grains can be a nutritious part of a regular diet, as well as possessing a therapeutic or preventive effect on various chronic disease conditions.

Cereal Grain Protein Health Benefits

  1. Top of page
  2. Abstract
  3. Introduction
  4. Cereal Storage Protein Description
  5. Cereal Health Benefits
  6. Cereal Grain Protein Health Benefits
  7. Predicted Biological Activity of Cereal Grain Peptides
  8. Concluding Remarks
  9. References

Cereal grain proteins have been shown to have favorable satiety and inhibitory effects in human and animal studies. One study compared the satiating effects of dairy and wheat proteins in rats and concluded that protein quality did not alter the overall appetite suppression observed among all rats, indicating that proteins inherently have certain physiological characteristics regardless of their quality or source (Bensad and others 2002). Wheat proteins were shown to be a good stimulator of cholecystokinin and glucagon-like peptide 1 (GLP-1) release when exposed to human duodenal tissue, which could encourage wheat protein use as a dietary ingredient in weight management (Geraedts and others 2010). Oat, barley, and wheat were shown to contain dipeptidyl peptidase-IV (DPP-IV)-inhibitor peptides in an in silico study (Lacroix and Li-Chan 2012). Recently, Velarde-Salcedo and others (2013) have shown in vitro the inhibitory activity of DPP-VI in wheat. Oat was also found to have proteins with ACE-inhibitory effects in silico and in vivo study (Cheung and others 2009).

Barley showed a variety of inhibitory effects when used as a barley protein isolate for fortification of wheat flour in bread (Alu'Datt and others 2012). When used at a maximum amount of 15%, the barley protein isolate showed a 75% ACE-inhibitory activity in bread. In 2010, a study conducted on hypercholesterolemic men and postmenopausal women compared the effects of barley protein and calcium caseinate on different markers of health (Jenkins and others 2010). Both protein sources had similar satiety results, as well as similar effects on serum lipids, antioxidant response, and blood pressure at the end of the treatment period, concluding that barley protein would be a suitable plant source of protein in the diet. Prolamins isolated from rice were found to have a greater antileukemia effect than wheat glutenins and gliadins without the added inflammatory effects from gluten (Chen and others 2010). Another study also showed rice bran peptides having strong cancer cell antiproliferative activities, almost maximum inhibition on colon, breast, and liver cancer cells (Kannan and others 2010). Nine cultivars of barley were shown to contain lunasin, a bioactive peptide with chemopreventive and anticancer effects (Jeong and others 2010). These barley sources of lunasin were proven bioactive and bioavailable in in vivo and in vitro studies (Jeong and others 2010).

Amaranth grain contains bioactive peptides; a study reported finding a lunasin-like peptide that showed cancer-preventative effects and inhibited histone acetylation in the nucleus of NIH-3T3 cells (Maldonado-Cervantes and others 2010). Amaranth peptides have shown, for the first time, to have high DPP-IV-inhibitor activity and antidiabetic potential (Velarde-Salcedo and others 2012), especially in peptides exposed to simulated gastrointestinal digestion (Velarde-Salcedo and others 2013). This also emphasizes the opportunity of the health benefits from these bioactive peptides to be gained from regular food consumption, rather than a formulated drug therapy. ACE-inhibitory peptides (ALEP, VIKP) and anti-hypertensive peptides (IKP, LEP) were also found in amaranth 11S globulin in an in silico study, which utilized 3D models and utilized simulated protein docking technologies (Vecchi and Anon 2009).

It is well known that a diet high in whole grains will reduce the risk of chronic disease, but what remains less clear is the full mechanism of action of these claims, as well as if any other nutrients, such as proteins, may have a synergistic effect that could contribute to the beneficial health results credited to other grain components, such as fiber and antioxidants (Jensen and others 2006).

Predicted Biological Activity of Cereal Grain Peptides

  1. Top of page
  2. Abstract
  3. Introduction
  4. Cereal Storage Protein Description
  5. Cereal Health Benefits
  6. Cereal Grain Protein Health Benefits
  7. Predicted Biological Activity of Cereal Grain Peptides
  8. Concluding Remarks
  9. References

We performed a scientific prediction of the bioactive peptides that may be potentially obtained from main proteins in wheat, barley, oat, and rice cereal grains. Analysis of cereal storage proteins for bioactive peptides was conducted for all the protein sequences reported and then evaluated for the profile of active peptides using the database http://www.uwm.edu.pl/biochemia. The cereal storage proteins contained many potential bioactive peptides. Figure 3 shows the amino acid sequence of C hordein in barley and all the different biological activities are mapped onto the sequence. The amount of protein fragments for each type of biological activity varied, but trends among the cereal proteins were observed, such as a high amount of ACE-inhibitor and DPP-IV-inhibitor fragments. The occurrence frequency (A) of bioactive fragments with a particular activity in a polypeptide chain was calculated by the equation: A = a/N. In the equation, a is the number of amino acid residues forming fragments with given activity in protein sequence, and N is the number of amino acid residues of the protein.

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Figure 3. Illustration of bioactive components found in barley storage protein C-hordein.

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Fifteen cereal storage proteins from wheat, oat, barley, and rice were analyzed for potential bioactivity using the BIOPEP database and the method outlined by Iwaniak and Dzibua (2011). Many different biological peptide sequences were found in the grain proteins, including inhibitors of DPP-IV. DPP-IV is an enzyme that cleaves peptides at position 2 of the N terminus of a peptide sequence containing either the amino acid alanine or proline (Thornberry and Gallwitz 2009). DPP-IV substrates in humans are the incretins GLP-1 and glucose-dependent insulinotropic peptide (GIP; Thornberry and Gallwitz 2009). GLP-1 is naturally therapeutic in managing glucose levels in blood, and thus effective in treating type-2 diabetes. Due to its rapid breakdown in the body by DPP-IV, GLP-1 cannot survive long enough in vivo to have any effect. Two options for diabetes treatment emerge; either use incretins that cannot be broken down by DPP-IV, or find a way to inhibit the enzyme itself and allow natural GLP-1 to circulate in the body.

Currently, multiple orally active competitive inhibitors are being studied in animal models of diabetes (Thornberry and Gallwitz 2009). DPP-IV inhibitors, such as linagliptin, have also been shown to be effective in lowering blood glucose levels and decreasing cardiovascular events in human trials (Gallwitz and others 2012); however, this DPP-IV inhibitor causes side effects such as weight gain. Prolyl endopeptidase (PEP; EC 3.4.21.26) is a cytosolic peptidase that has been found to degrade neuropeptides found in the central nervous system, such as oxytocin (Heim and others 2012). Altered PEP levels have been found in human patients with psychological diseases, such as autism spectrum disorders (Momeni and others 2005). Naturally derived peptide inhibitors of this enzyme could potentially help maintain psychological health and prevent future damage. These types of inhibitions are just two of the biological activities that these cereal grain peptides are shown to have.

The storage proteins of wheat are listed in Table 1 and include LMW glutenin, HMW glutenin, alpha-, gamma-, and omega-gliadin. The biological activities of wheat storage proteins are shown in Table 2-6. LMW glutenin was high in ACE inhibitors, general inhibitors such as DPP-IV, and celiac toxic peptides. LMW glutenin also contained a small amount of opioids (A = 0.003), which could act as analgesics or as antioxidant peptides (A = 0.0206). HMW glutenin was also high in ACE-inhibitor peptides, as well as opioid, antithrombotic, DPP-IV inhibitor, and had the highest occurrence frequency of antioxidant peptides out of all the wheat proteins studied. HMW glutenin also contained some anticancer peptide sequences (A = 0.006). Alpha-gliadin contained high amounts of ACE inhibitors, as well as DPP-IV and PEP inhibitors. It was also one of the few proteins evaluated in this investigation that had some neuropeptide activity. Both gamma- and omega-gliadin had similar occurrence frequencies of ACE-inhibitor, DPP-IV-inhibitor, and antioxidant peptides, though omega-gliadin was higher in celiac toxic peptides, while gamma-gliadin contained some hypotensive (rennin-inhibitor) and DPP-IV-inhibitor peptides. Overall, the wheat storage proteins contained a variety of bioactive peptides with many different activities within the body, including anticancer and antioxidant effects, and DPP-IV, ACE, and PEP inhibitors.

Table 2. Predicted wheat protein biological activity in LMW glutenin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0052VPLDiprotin BMaruyama and others 1996
ACE inhibitor0.2397IR, LY, IY, VF, VY, PR, LAA, LQP, LNP, IRA, LQQ, YSQQQQ, PLG, PL, IA, IP, LA, VP, RA, AA, VG, IG, GI, GV, GQ, GT, HG, QG, LG, SF, AR, FAL, EV, LQ, LN, TQ, AH, PP, PQ, HP, PH, IQY, TF, AIACE inhibitorNogata and others 2009
Celiac toxic0.0490QQQP, QQQQPPFSQQQQSPFSQQQQGluten T-cell epitopeDewar and others 2004
Antibacterial0.0026IQYActive against gram-positive bacteriaLopez-Exposito and others 2006
Opioid0.0026PLGAnalgesicFukudome and Yoshikawa 1992
Stimulating0.0258VPL, VL, LV, IL, LI, II, LLStimulating vasoactive substance release and glucose uptakeRingseis and others 2005; Morifuji and others 2009
Antioxidant0.0206LY, IY, AH, PHQ, RHE, IQY, IR, VYOxygen radical-scavengingHuang and others 2010
Inhibitor0.0876GQ, PP, VA, LA, FA, LP, VP, LL, PPPF, IRDPP-IV inhibitorBella and others 1982
Hypotensive0.0026IRRenin inhibitorLi and Aluko 2010
Activating ubiquitin-mediated proteolysis0.0129RA, LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 3. Predicted wheat protein biological activity in HMW glutenin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0124PGPEP inhibitorAshmarin and others 1998
ACE inhibitor0.3540RL, PQR, RY, IPA, VPP, VSP, LAA, FY, YP, LQQ, LKA, IP, LA, KR, VP, AA, IF, GI, AG, KG, DA, GQ, GT, WG, GE, GG, GD, EG, EA, PG, PPK, SY, KA, VE, LQ, PP, PQ, ME, HP, TF, VVPPACE inhibitorNogata and others 2009
Antithrombotic0.0186PG, PPKInhibit blood platelet aggregationAshmarin and others 1998
Opioid0.0248YYP, RYYP, SYYPAnalgesicFukudome and Yoshikawa 1992
Stimulating0.0186IV, LL, SEStimulating vasoactive substance release and glucose uptakeMorifuji and otehrs 2009; Ringseis and others 2005
Regulating0.0124PGRegulating stomach mucosal membrane activityAshmarin and others 1998
Anticancer0.0062VVVDvl-protein bindingLee and others 2009
Antioxidant0.0497EL, RYY, SYY, LKOxygen radical-scavengingHuang and others 2010
Inhibitor0.1118GQ, PP, VA, KA, LA, PA, LP, VP, LL, VV, IPADPP-IV inhibitorBella and others 1982
Activating ubiquitin-mediated proteolysis0.0062LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 4. Predicted wheat protein biological activity in alpha-gliadin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0064VPL, PGDiprotin B & PEP inhibitorMaruyama and others 1996; Ashmarin and others 1998
ACE inhibitor0.3131IR, FQP, PYP, VY, FP, IPP, LQP, LNP, YL, YP, LQQ, PL, IA, IP, RP, AP, LA, VP, IF, GI, FG, GS, GQ, GT, QG, PG, VR, IFG, SF, KY, IAP, EI, LQ, LN, AH, PP, PQ, PH, TF, AIACE inhibitorNogata and others 2009
Celiac toxic0.0895PSQQQP, YPQPQ, YPQPQPF, QQPYPQ, QQQP, PSQQ, QQPY, QPYP, QPQPFPSQQPYLQL, QPFPSQQPYLQLQP, PSQQQPQEQVPL, QEQVPLVQQQQF, FPPQQPYPQPQP, YPQPQPFPSQQP, FPSQQPYLQLQP, QILQQILQQIL, QGSVQPQQLPQF, ALQTLPAMCNVY, IAPFGIFGTN, SSQVSFQPSQLN, PQPQPFPSQQPYGluten T-cell epitopeDewar and others 2004
Antithrombotic0.0032PGInhibit blood platelet aggregationAshmarin and others 1998
Stimulating0.0415VPL, VL, LV, IL, LI, II, LLStimulating vasoactive substance release & glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Neuropeptide0.0064YLAnxiolyticKanegawa and others 2010
Regulating0.0032PGRegulating stomach mucosal membrane activityAshmarin and others 1998
Antioxidant0.0224AH, PYPQ, IR, TY, VYOxygen radical-scavengingAshmarin and others 1998
Inhibitor0.0927GQ, PP, VA, LA, FA, AP, FP, PA, LP, VP, LL, VV, HA, IRDPP-IV inhibitorBella and others 1982
Hypotensive0.0032IRRenin inhibitorLi and Aluko 2010
Stimulating different activities0.0032PQPFPSQQPYLQStimulating g-interferon production peptideCornell and others 1994
Activating ubiquitin-mediated proteolysis0.0064LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 5. Predicted wheat protein biological activity in gamma-gliadin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0035VPLDiprotin BMaruyama and others 1996
ACE inhibitor0.3298ILP, IR, PQR, LW, LVL, VY, FP, VPP, PR, LNP, IRA, YP, LQQ, PL, IP, RP, AP, LA, VP, RA, AA, VG, IG, GI, AG, GV, GQ, GT, GG, QG, YVP, NF, SF, KP, EV, LQ, LN, TQ, PP, PQ, PH, IQP, TF, AIACE inhibitorNogata and others 2009
Celiac toxic0.0461QQQP, QPQQSFPQQQ, PFPQPQQQF, PFPQQPQQT, PFPQTQQPQ, PQQQFPQPQ, QFPQPQQPQ, QQTYPQRPQ, QRPQQPFPQ, QTQQPQQPF, IQPQQPFPQ, VQGQGILQPQQPAQLT-cell epitopeDewar and others 2004
Stimulating0.0496VPL, VL, LV, IV, IL, LI, II, LLStimulating vasoactive substance release and glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Antioxidant0.0390LWS, PHQ, AQIPQQ, VPW, PW, IR, KP, TY, VYOxygen radical-scavengingHuang and others 2010
Inhibitor0.0922GQ, PP, VA, LA, FA, AP, FP, PA, LP, VP, LL, IRDPP-IV inhibitorBella and others 1982
Hypotensive0.0071IRRenin inhibitorLi and Aluko 2010
Activating ubiquitin-mediated proteolysis0.0106RA, LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 6. Predicted wheat protein biological activity in omega-gliadin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

ACE inhibitor0.4000QPIP, PYP, FP, LQP, LNP, LF, YG, YP, LQQ, LAMA, PL, IA, IP, LA, AA, IF, IG, GS, GQ, GG, SY, SF, NK, AR, LQ, LN, PT, TQ, PQ, KE, IQP, TFACE inhibitorNogata and others 2009
Celiac toxic0.1179QQPYPQ, QQQP, PSQQ, QQPY, QPYP, QQPQQPFPL, PFPQPQLPF, PFPQPQQPI, PQPQLPFPQ, PQPQQPIPV, PYPQQPYPS, QQPYPQQPY, QQPFPQQPY, PFPQQPYPQ, PQPQQPFPW, QQPIPQQPQ, IQPQQPFPQ, QQPFPQQPQQPFPQ, QQPFPQQPQQPFPQGluten T-cell epitopeDewar and others 2004
Immunomodulating0.0036YGEnhancing protein biosynthesis in lymphocytesKayser and Meisel 1996
Stimulating0.0179VL, LI, II, LL, SEStimulating vasoactive substance release and glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Antioxidant0.0286EL, PYPQ, PWQ, PEL, PWOxygen radical-scavengingHuang and others 2010
Inhibitor0.0929GQ, MA, LA, FA, FP, LP, LLDPP-IV inhibitorBella and others 1982
Activating ubiquitin-mediated proteolysis0.0036LAControls concentration of intracellular regulatory proteinsTurner and others 2000

The major oat storage proteins that were reviewed are presented in Table 7. It includes 11S globulin, 12S globulin, and Avenin N9. The biological activities of oat storage proteins are shown in Table 8-10. Both globulins had similar occurrence frequencies of ACE-inhibitor, antiamnestic (PEP-inhibitor), DPP-IV-inhibitor, antioxidant, and hypotensive peptides. Both globulins contained antithrombotic peptides and also bacterial permease ligand activity, which differed from other storage proteins analyzed. Avenin N9, unlike the globulins, contained a lower occurrence frequency of ACE-inhibitor and antioxidant peptides, but it contained opioid and celiac toxic activity. It also had a similar level of DPP-IV-inhibitor peptides. Knowing that oat is often used as a wheat alternative for people with celiac disease, it was surprising to see celiac toxic peptides in this particular protein.

Table 7. Oat seed storage proteins
   Amin acid 
Oat proteinIDSequenceresiduesMolecular mass
  1. Protein sequence was obtained from BIOPEP database.

11S Globulin1464MATTSFPSMLFYFCIFLLFHGSMAQLFGQSSTPWQSSRQGGLRGCRFDRLQAFEPLRQVRSQAGITEYFDEQNEQFRCTGVSVIRRVIEPQGLVLPQYHNAPALVYILQGRGFTGLTFPGCPATFQQQFQPFDQSQFAQGQRQSQTIKDEHQRVQRFKQGDVVALPAGIVHWCYNDGDAPIVAIYVFDVNNNANQLEPRQKEFLLAGNNKREQQSGNNIFSGLSVQLLSEALGISQQAAQRIQSQNDQRGEIIRVSQGLQFLKPIVSQQVPGEQQVYQPIQTQEGQATQYQVGQSTQYQVGKSTPYQGGQSSQYQAGQSWDQSFNGLEENFCSLEARKNIENPQHADTYNPRAGRITRLNSKNFPILNIVQMSATRVNLYQNAILSPFWNINAHSVIYMIQGHARVQVVNNNGQTVFNDILRRGQLLIVPQHFVVLKKAEREGCQYISFKTNPNSMVSHIAGKSSILRALPIDVLANAYRISRQEARNLKNNRGEEFGAFTPKLTQKGFQSYQDIEEGSSSPVRASE52759,523.8610
12S Globulin1167QLFGQSFTPWQSSRQGGLRGCKFDRLQAFEPLRQVRSQAGITEYFDEQNEQFRCAGVSVIRRVIEPQGLLLPQYHNAPGLVYILQGRGFTGLTFPGCPATFQQQFQQFDQARFAQGQSKSQNLKDEHQRVHHIKQGDVVALPAGIVHWCYNDGDAPIVAVYVFDVNNNANQLEPRQKEFLLAGNNKREQQFGQNIFSGFSVQLLSEALGISQQAAQKIQSQNDQRGEIIRVSQGLQFLKPFVSQQGPVEHQAYQPIQSQQEQSTQYQVGQSPQYQEGQSTQYQSGQSWDQSFNGLEENFCSLEARQNIENPKRADTYNPRAGRITHLNSKNFPTLNLVQMSATRVNLYQNAILSPYWNINAHSVMHMIQGRARVQVVNNHGQTVFNDILRRGQLLIIPQHYVVLKKAEREGCQYISFKTTPNSMVSYIAGKTSILRALPVDVLANAYRISRQESQNLKNNRGEEFGAFTPKFAQTGSQSYQDEGESSSTEKASE49455,976.5760
N9 Avenin1462TTTVQYNPSEQYQPYPEQQEPFVQQQPFVQQQQQPFVQQQQMFLQPLLQQQLNPCKQFLVQQCSPVAVVPFLRSQILRQAICQVARQQCCRQLAQIPEQLRCPAIHSVVQAIILQQQQQQQFFQPQLQQQVFQPQLQQVFNQPQQQAQFEGMRAFALQALPAMCDVYVPPQCPVATAPLGGF18220,211.0879
Table 8. Predicted oat protein biological activity in 11S globulin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0076LSPFWNINA, SPFWNINA, PGPEP inhibitorAshmarin and others1998
ACE inhibitor0.3207VLP, RL, IR, FQP, LY, IY, VF, LVL, GDAP, RF, FWN, VY, FP, PR, LSP, LF, FY, AY, PL, LKP, IA, AF, AP, LA, KR, VP, RA, AA, GF, FR, IF, VG, GI, GA, GL, AG, GH, GR, KG, FG, DA, GS, GV, GQ, GK, HG, GE, GG, QG, SG, LG, GD, TG, EG, EA, NG, PG, VR, LTF, TNP, QK, DG, NF, SY, SF, KL, NK, RR, AR, KA, VIY, EY, LLF, KP, EI, IE, TE, LQ, LN, TQ, AH, PQ, KE, IEP, TF, AIACE inhibitorNogata and others 2009
Antithrombotic0.0038PGInhibit blood platelet aggregationAshmarin and others 1998
Stimulating0.0512SSS, VL, LV, IV, IL LI, II, LL, EE, SEStimulating vasoactive substance release and glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Regulating0.0038PGRegulating stomach mucosal membrane activityAshmarin and others 1998
Antioxidant0.0342AY, LY, IY, AH, PWQ, KD, PW, IR, LKP, LK, KP, TY, VYOxygen radical-scavengingHuang and others 2010
Bacterial permease ligand0.0019KKInvolved in protein bindingSleigh and others 1997
inhibitor0.0797GQ, VA, MA, KA, LA, FA, AP, FP, PA, LP, VP, LL, VV, HA, IR, EFDPP-IV inhibitorBella and others 1982
Hypotensive0.0076IR, EFRenin inhibitorLi and Aluko 2010
Activating ubiquitin-mediated proteolysis0.0095RA, LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 9. Predicted oat protein biological activity in 12S globulin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0061PG, GPPEP inhibitorAshmarin and others 1998
ACE inhibitor0.3219RL, IR, LY, VF, GDAP, YW, RF, VY, HY, FP, PR, LSP, LF, AY, LLP, PGL, GP, PL, GPV, LKP, IA, IP, AF, AP, LA, KR, RA, AA, GF, FR, IF, VG, GI, GA, GL, AG, HL, GR, FG, DA, GS, GV, GQ, GK, HG, GE, GG, QG, SG, LG, GD, TG, EG, EA, NG, PG, VR, VAV, LTF, QK, DG, NF, SY, SF, KF, NK, RR, AR, KA, EY, KP, EI, IE, VE, TE, LQ, LN, PT, TQ, AH, PQ, EK, KE, IEP, TF, AIACE inhibitorNogata and others 2009
Antithrombotic0.0061GP, PGInhibit blood platelet aggregationAshmarin and others 1998
Stimulating0.0486SSS, LLL, VL, LV, IV, IL, LI, II, LL, EE, SEStimulating vasoactive substance release and glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Regulating0.0061GP, PGRegulating stomach mucosal membrane activityAshmarin and others 1998
Antioxidant0.0425HL, HH, VHH, AY, LY, AH, PWQ, KD, PW, IR, LKP, LK, KP, TY, VYOxygen radical-scavengingHuang and others 2010
Bacterial permease ligand0.0020KKInvolved in protein bindingSleigh and others 1997
inhibitor0.0810GQ, GP, VA, KA, LA, FA, AP, FP, PA, LP, LL, VV, IR, KF, EFDPP-IV inhibitorBella and others 1982
Hypotensive0.0121IR, KF, EFRenin inhibitorLi and Aluko 2010
Activating ubiquitin-mediated proteolysis0.0121RA, LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 10. Predicted oat protein biological activity in avenin N9
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

ACE inhibitor0.2802FQP, PYP, VF, MF, TAP, VY, VPP, LQP, LNP, FNQ, YP, LQQ, PLG, PL, IP, AF, AP, LA, VP, RA, GF, GM, GG, LG, EG, YVP, VAV, AR, FAL, LQ, LN, PP, PQ, AIACE inhibitorNogata and others 2009
Celiac toxic0.0220QQQP, QPYP, QYQPYPEQQEPFVQGluten T-cell epitopeDewar and others 2004
Opioid0.0055PLGAnalgesicFukudome and Yoshikawa 1992
Stimulating0.0330LV, IL, II, LL, SEStimulating vasoactive substance release and glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Antioxidant0.0055VYOxygen radical-scavengingHuang and others 2010
Inhibitor0.0824PP, VA, LA, FA, AP, PA, LP, VP, LL, VVDPP-IV inhibitorBella and others 1982
Activating ubiquitin-mediated proteolysis0.0110RA, LAControls concentration of intracellular regulatory proteinsTurner and others 2000

The major storage proteins of barley are listed in Table 11 and include B-hordein precursor, C-hordein, D-hordein, and globulin. The biological activities of barley storage proteins are shown in Table 12-15. The B-hordein precursor contained a high amount of ACE inhibitors, as well as PEP and DPP-IV-inhibitor peptides. This protein also had a moderate amount of celiac toxic peptides and some antibacterial and antithrombotic activity. C-hordein also had similar levels of ACE-inhibitor, DPP-IV-inhibitor, and celiac toxic peptides, though it also contained some neuropeptide (anxiolytic) activity. D-hordein had the highest occurrence frequency of ACE-inhibitor peptides of all the barley proteins (A = 0.511) and also showed opioid (peptides GYYP, GYY, WYYP, YYP) inhibitor, and DPP-IV-inhibitor activity (peptides GQ, GP, PP, VA, MA, KA, LA, AP, FP, PA, LP, VP, LL, VV). Barley hordeins had higher occurrence frequencies of antioxidant activity than the other storage proteins studied. Like C-hordein, barley globulin had ACE- and DPP-IV-inhibitor peptide activity, though it had the lowest amount of antioxidant activity among the barley proteins (A = 0.009). Generally, the barley hordeins tended to have higher occurrence frequencies of antioxidant activity (0.0375 in B-hordein, 0.0355 in C-hordein, and 0.0555 in D-hordein) than the other storage proteins studied. Wheat proteins had an average antioxidant occurrence frequency of 0.0321, oat proteins of 0.0274, rice of 0.0325, and barley proteins of 0.0344, with the average of the hordeins being 0.0428. However, the highest single protein occurrence frequency of antioxidant activity was HMW glutenin with 0.0497.

Table 11. Barley seed storage proteins
   Amino acid 
Barley proteinIDSequenceresiduesMolecular mass
B-hordein precursor1603MKTFLIFALLAIAATSTIAQQQPFPQQPIPQQPQPYPQQPQPYPQQPFPPQQPFPQQPVPQQPQPYPQQPFPPQQPFPQQPPFWQQKPFPQQPPFGLQQPILSQQQPCTPQQTPLPQGQLYQTLLQLQIQYVHPSILQQLNPCKVFLQQQCSPVPVPQRIARSQMLQQSSCHVLQQQCCQQLPQIPEQFRHEAIRAIVYSIFLQEQPQQLVEGVSQPQQQLWPQQVGQCSFQQPQPQQVGQQQQVPQSAFLQPHQIAQLEATTSIALRTLPMMCSVNVPLYRILRGVGPSVGV29332,597.4199
C-hordein1627MKTFLTFVLLAMVMSIVTTARQLNPSSQELQSPQQSYLQQPYPQNPYLPQQPFPVQQPFHTPQQYFPYLPEELSPQYQIPTPLQPQQPFPQQPQQPLPRPQQPFPWQPQQPFPQPQQPIPYQPQQPFNQQPQQIISQQPQQPFPQQPQQPFPQPQQPFPWQPQQPFPQPQQPFPLQPQQPFPWQPQQPFPQPQQPIAHQPQQPFSFSQQPQQPFPLQPQQPFPQQPQQPFPQQPQQIIFQQPQQSYPVQPQQPFPQPQPVPQQRPQQASPLQPQQPFPQGSEQIIPQQPQQPFPLQPHQPYTQQTIWSMV31036,508.2031
D-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,378.3906
Globulin1634MGKFIFFAVFLTTLVTISAAQGVLEQSLADAQCRGEVQAKPLLACRQILEHQLTGRAVGVRPFQAQWGARDRCCQQLESVSRGCRCSALRGMVRDYEQSMPPLREGRRRSSGERQQEQGCSGESTAEQQQEVQGGQYGSETGESQQQQGGGYHGVTVGRGGQQQGQMLCRERPQRQQQGEGFSGEGAQQKPKVGRVRLTKVRLPTACRIEPQECSVFSTLPVLG22423,529.3379
Table 12. Predicted barley protein biological activity in B-hordein precursor
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0068VPL, GPDiprotin B & PEP inhibitorMaruyama and others 1996; Ashmarin and others 1998
ACE inhibitor0.4096QPIP, PLP, IR, PYP, PQR, LY, VF, LW, VY, FP, LQP, LNP, IRA, YP, LQQ, GP, PL, IVY, IA, IP, AF, LA, VP, RA, AA, FR, IF, VG, GL FG, GV, GQ, QG, EG, EA, QK, SF, AR, LVE, KP, FAL, VE, LQ, LN, PP, PQ, HP, PH, IQY, TF, AIACE inhibitorNogata and others 2009
Celiac toxic0.0478QQQP, QPYP, PFPQQPIP, PIPQQPQPY, PQPYPQQPF, PQPYPQQPQ, PYPQQPQPY, QQPFPQQPI, QQPFPQQPV, QQPIPQQPQGluten T-cell epitopeDewar and others 2004
Antibacterial0.0034IQYActive against gram-positive bacteriaLopez-Exposito and others 2006
Antithrombotic0.0034GPInhibit blood platelet aggregationAshmarin and others 1998
Stimulating0.0341VPL, LV, IV, IL, LI, LLStimulating vasoactive substance release and glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Regulating0.0034GPRegulating stomach mucosal membrane activityAshmarin and others 1998
Antioxidant0.0375LY, PYPQ, PHQ, RHE, IQY, IR, KP, VYOxygen radical-scavengingHuang and others 2010
Inhibitor0.0819GQ, GP, PP, LA, FA, FP, LP, VP, LL, IRDPP-IV inhibitorBella and others 1982
Hypotensive0.0034IRRenin inhibitorLi and Aluko 2010
Activating ubiquitin-mediated proteolysis0.0068RA, LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 13. Predicted barley protein biological activity in C-hordein
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

ACE inhibitor0.3774QPIP, PLP, PYP, FP, PR, LSP, LQP, LNP, YL, FNQ, YP, LQQ, PL, IW, IA, IP, RP, LA, VP, IF, GS, QG, LTF, SY, SF, AR, IPY, LQ, LN, PT, TQ, AH, PQ, PH, TFACE inhibitorNogata and others 2009
Celiac toxic0.0516QQPYPQ, QQPY, QPYP, QQPQQPFPL, PFPQPQQPI, PLPRPQQPF, PRPQQPFPW, QQPQQPLPR, PQPQQPFPW, PFPQQPQQI, QQPFPQQPQQPFPQ, QQPFPQQPQQPFPQGluten T-cell epitopeDewar and others 2004; Fukudome and Yoshikawa 1992
Stimulating0.0258VL, IV, II, LL, EE, SEStimulating vasoactive substance release and glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Neuropeptide0.0097YLAnxiolyticKanegawa and others 2010
Antioxidant0.0355AH, EL, PYPQ, PHQ, PWQ, PWOxygen radical-scavengingHuang and others 2010
Contracting0.0032PLPRIleum-contracting peptideTakahashi and others 1996
Inhibitor0.0774LA, FP, LP, VP, LLDPP-IV inhibitorBella and others 1982
Activating ubiquitin-mediated proteolysis0.0032LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 14. Predicted barley protein biological activity in D-hordein
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0304PG, GPPEP inhibitorAshmarin and others 1998
ACE inhibitor0.5112RL, PYP, LY, KW, TAP, LVL, HY, FP, GY, VSP, LQP, LF, YG, FY, AY, YP, LQQ, GP, PL, VK, IA, GW, RP, AP, LA, KR, VP, AA, GF, IF, VG, GA, GL, GH, KG, FG, GS, GQ, GK, GT, WG, HG, GE, GG, QG, SG, LG, TG, EG, EA, NG, PG, VR, VAV, QK, SY, SF, RR, KA, KP, EI, EV, VE, TE, LQ, TQ, PP, PQ, HP, PH, TF, AIACE inhibitorNogata and others 2009
Antithrombotic0.0304GP, PGInhibit blood platelet aggregationAshmarin and others 1998
Immunomodulating0.0013YGEnhancing protein biosynthesis in lymphocytesKayser and Meisel 1996
Opioid0.0198GYYP, YYP, GYY, WYYPAnalgesicFukudome and Yoshikawa 1992
Stimulating0.0092VL, LV, IV, LLStimulating glucose uptakeMorifuji and others 2009
Regulating0.0304GP, PGRegulating stomach mucosal membrane activityAshmarin and others 1998
Antioxidant0.0555LHH, LH, HH, AY, GYY, LY, EL, WY, YYG, LYY, WYY, LHQ, PHQ, PWS, LQPGQGQQ, LQPGQGQQG, PW, LK, KPOxygen radical-scavengingHuang and others 2010
Inhibitor0.1136GQ, GP, PP, VA, MA, KA, LA, AP, FP, PA, LP, VP, LL, VVDPP-IV inhibitorBella and others 1982
Activating ubiquitin-mediated proteolysis0.0026LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 15. Predicted barley protein biological activity in globulin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

ACE inhibitor0.3795RL, PQR, VF, VRP, GGY, GY, YG, PL, RP LA, RA, AA, GF, IF, VG, GM GA, GR, DA, GS, GV, MG, GQ, GK WG, HG, GE, GG, QG, SG, LG, TG, EG, VR, QK, KF, RR, AR, KP, IE, EV, PT, PP, PQ, IEPACE inhibitorNogata and others 2009
Antithrombotic0.0045SSGEInhibit blood platelet aggregationAshmarin and others 1998
Immunomodulating0.0045YGEnhancing protein biosynthesis in lymphocytesKayser and Meisel 1996
Stimulating0.0268VL, LV, IL, LL, SEStimulating vasoactive substance release and glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Regulating0.0045DYRegulating ion flowZiganshin and others 1994
Antioxidant0.0089KPOxygen radical-scavengingHuang and others 2010
Inhibitor0.0536GQ, PP, MP, LA, FA, LP, LL, KFDPP-IV inhibitorBella and others 1982
Hypotensive0.0045KFRenin inhibitorLi and Aluko 2010
Activating ubiquitin-mediated proteolysis0.0134RA, LAControls concentration of intracellular regulatory proteinsTurner and others 2000

The storage proteins of rice are shown in Table 16 and include a 13-kDa prolamin, rice glutelin, and rice 16-kDA prolamin. The biological activities of rice storage proteins are shown in Table 17-19. The 13-kDa prolamin highest level of biological activity was due to ACE-inhibitor peptides, like the other proteins studied, and it also contained some DPP-IV-inhibitor activity as well. This protein was lower in diversity of biological activities compared to other proteins studied; only containing sequences that matched 5 different types of activity. The glutelin protein had much more abundant activity, including antiamnestic, antithrombotic, anticancer, DPP-IV-inhibitor, and neuropeptide activity. Glutelin also showed a high occurrence frequency of ACE-inhibitor peptides. Unlike any of the other proteins analyzed, it was the only protein to have embryotoxic activity (A = 0.004), which was associated with the RGD amino acid sequences. The rice 16-kDA prolamin had mostly ACE-inhibitor peptide sequences, as well as some hypotensive, antioxidant, and DPP-IV-inhibitor activity. Though the rice proteins had some of the lowest diversity among different potential bioactivities, rice also contained a unique peptide sequence, RGD, found in the glutelin storage protein (Table 18). RGD stands for the amino acid sequence arginine-glycine-aspartic acid and this peptide is commonly found in legumes, such as soybean and others (Cam and de Mejia 2012). The RGD motif has been linked to several bioactive properties, including anti-inflammatory activity, anti-angiogenic activity, and even it has been shown to affect integrin-mediated responses in cells and prevent cardiovascular disease (Cam and de Mejia 2012). This indicates that the proteins found in rice could have beneficial health properties not seen in the other cereal grain storage proteins analyzed. Peptides are complex biomolecules that have unique chemical and physical properties as a direct result of their amino acid composition and amino acid sequence. On how the amino acid sequences in peptides may influence their functionality is extremely interesting to observe based on the results in Table 2-6, 8-10, 12-15, and 17-19.

Table 16. Rice seed storage proteins
   Amin acid 
Rice proteinIDSequenceresiduesMolecular mass
  1. Protein sequence was obtained from BIOPEP database.

13-kDA prolamin1581MKIIFRLCSPCYCCMQHLCVVDVLGQSYRQYQLQSPLLQQQQVLSPYNDFVRQRYGIAASPFLQSAAFKLRNNQVWQQLGLVAQQSHYQDINIVQAIAQQL10111,206.8926
Glutelin1593MASMSTILPLCLGLLLFFQVSMAQFSFGGSPLQSPRGFRGDQDSRHQCRFEHLTALEATHQQRSEAGFTEYYNIEARNEFRCAGVSVRRLVVESKGLVLPMYANAHKLVYIVQGRGVFGMALPGCPETFQSVRSPFEQEVATAGEAQSSIQKMRDEHQQLHQFHQGDVIAVPAGVAHWLYNNGDSPVVAFTVIDTSNNANQLDPKRREFFLAGKPRSSWQQQSYSYQTEQLSRNQNIFAGFSPDLLSEALSVSKQTVLRLQGLSDPRGAIIRVENGLQALQPSLQVEPVKEEQTQAYLPTKQLQPTWLRSGGACGQQNVLDEIMCAFKLRKNIDNPQSSDIFNPHGGRITRANSQNFPILNIIQMSATRIVLQNNALLTPHWTVNAHTVMYVTAGQGHIQVVDHRGRSVFDGELHQQQILLIPQNFAVVVKARREGFAWVSFKTNHNAVDSQIAGKASILRALPVDVVANAYRLSREDSRHVKFNRGDEMAVFAPRRGPQQYAEWQINEK51057,221.0160
16-kDA prolamin1592MKIIFFFALLAIAACSASAQFDAVTQVYRQYQLQPHLMLQQQMLSPCGEFVRQQCSTVATPFFQSPVFQLRNCQVMQQQCCQQLRMIAQQSHCQAISSVQAIVQQLRLQQFASVYFDQSQAQAQAMLALNMPSICGIYPSYNTAPCSIPTVGGIWY15616,634.2246
Table 17. Predicted rice protein biological activity in13-kDA prolamin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

ACE inhibitor0.2772RL, RY, VW, HY, LSP, YG, LQQ, PL, IA, AF, AA, FR, IF, GI, GL, HL, GQ, LG, VR, SY, KL, LQ, AIACE inhibitorNogata and others 2009
Immunomodulating0.0099YGEnhancing protein biosynthesis in lymphocytesKayser and Meisel 1996
Stimulating0.0594VL, LV, IV, II, LLStimulating glucose uptakeMorifuji and others 2009
Antioxidant0.0099HLOxygen radical-scavengingHuang and others 2010
Inhibitor0.0396GQ, VA, LL, VVDPP-IV inhibitorBella and others 1982
Table 18. Predicted rice protein biological activity in glutelin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

Antiamnestic0.0039PG, GPPEP inhibitorAshmarin and others 1998
ACE inhibitor0.3392ILP, VLP, RL, IR, AVP, LY, VF, MY, FAP, LVL, RF, VY, FP, GKP, PR, LQP, YL, LF, AY, LPG, GP, PL, AW, VK, FFL, IA, IP, AF, AP, LA, KR, VP, RA, YA, GF, FR, IF, GM, GA, GL, AG, GH, HL, GR, KG, FG, GS, GV, GQ, GK, HG, GE, GG, QG, SG, LG, GD, EG, EA, NG, PG, VR, QK, DG, NF, SY, SF, KF, KL, RR, AR, KA, EY, LLF, KP, EI, IE, EV, VE, TE, LQ, LN, PT, TQ, AH, PQ, EW, EK, KE, PH, HK, TF, AI, VRSPACE inhibitorNogata and others 2009
Antithrombotic0.0039GP, PGInhibit blood platelet aggregationAshmarin and others 1998
Stimulating0.0490LLL, VL, LV, IV, IL, LI, II, LL, EE, SEStimulating vasoactive substance release & glucose uptakeMorifuji and others 2009; Ringseis and others 2005
Neuropeptide0.0020YLAnxiolyticKanegawa and others 2010
Regulating0.0039GP, PGRegulating stomach mucosal membrane activityAshmarin and others 1998
Antioxidant0.0490LH, HL, AHK, AY, LY, AH, EL, EYY, YYN, YSY, LHQ, PHG, PHW, RHQ, RHV, MY, IR, KP, VYOxygen radical-scavengingHuang and others 2010
Inhibitor0.0824GQ, GP, VA, MA, KA, LA, FA, AP, FP, PA, LP, VP, LL, VV, IR, KF, EFDPP-IV inhibitorBella and others 1982
Hypotensive0.0078IR, KF, EFRenin inhibitor 
Anticancer0.0020VVVDvl protein bindingLee and others 2009
Embryotoxic0.0039RGDLaminin-like peptide involved in immune-mediated reproductive failureChambers and others 1995
Activating ubiquitin-mediated proteolysis0.0059RA, LAControls concentration of intracellular regulatory proteinsTurner and others 2000
Table 19. Predicted rice protein biological activity in 16-kDA prolamin
 OccurrenceSequences with  
Activityfrequencybiological activityDescriptionReferences
  1. Bioactive peptide sequence was obtained from BIOPEP database.

ACE inhibitor0.2756IYP, RL, IY, VF, TAP, VY, LSP, LQP, YP, LQQ, TQVY, IW, PSY, IA, IP, AP, LA, AA, IF, VG, GI, HL, DA, GE, GG, VR, SY, FAL, LQ, LN, PT, TQ, PH, AIACE inhibitorNogata and others 2009
Stimulating0.0192IV, II, LLStimulating glucose uptakeMorifuji and others 2009
Antioxidant0.0385HL, IY, WY, PHL, VYOxygen radical-scavengingHuang and others 2010
Inhibitor0.0577MP, VA, LA, FA, AP, LL, EFDPP-IV inhibitorBella and others 1982
Hypotensive0.0064EFRenin inhibitorLi and Aluko 2010
Activating ubiquitin-mediated proteolysis0.0128LAControls concentration of intracellular regulatory proteinsTurner and others 2000

The frequency of occurrence of the identified bioactive peptides in each of the cereal proteins was plotted on the y-axis, the type of proteins on the x-axis, and the activities on the z-axis following the methodology described by Silva-Sanchez and others (2008), as shown in Figure 4 and 5. The occurrence frequency of each storage protein in a particular cereal was compared to the other storage proteins, thus showing the bioactive potential of each cereal. Figure 4 and 5 define all the biological activities found for each protein in that particular cereal grain, and each cereal figure only shows the actual biological activities found in those specific cereal proteins. Blank spaces in figures reflect an absence of a particular biological activity.

image

Figure 4. Cereal grain bioactive peptides for (A) wheat and (B) oat. We performed a scientific prediction of bioactive peptides potentially present in main proteins in wheat and oat. First of all, we identified the protein sequences reported and then evaluated the profile of active peptides using the database http://www.uwm.edu.pl/biochemia. The occurrence frequency (A) of bioactive fragments with a particular activity was calculated by the equation: A = a/N, where a is the number of amino acid residues forming fragments with given activity in protein and N is the number of amino acid residues of the protein.

Bioactivity legend: A, ACE inhibitor; B, antiamnestic; C, antithrombotic; D, stimulating; E, regulating; F, antioxidant; G, bacterial permease ligand; H, DPP-IV inhibitor; I, hypotensive; J, activated ubiquitin-mediated proteolysis; K, celiac toxic; L, opioid; M, immunomodulating; N, neuropeptide; O, contracting; P, antibacterial; Q, stimulated different activities; R, anticancer; S, embryotoxic.

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image

Figure 5. Cereal grain bioactive peptides for (A) barley and (B) rice. We performed a scientific prediction of bioactive peptides potentially present in main proteins in wheat and oat. First of all, we identified the protein sequences reported and then evaluated the profile of active peptides using the database http://www.uwm.edu.pl/biochemia. The occurrence frequency (A) of bioactive fragments with a particular activity was calculated by the equation: A = a/N, where a is the number of amino acid residues forming fragments with given activity in protein and N is the number of amino acid residues of the protein.

Bioactivity legend: A, ACE inhibitor; B, antiamnestic; C, antithrombotic; D, stimulating; E, regulating; F, antioxidant; G, bacterial permease ligand; H, DPP-IV inhibitor; I, hypotensive; J, activated ubiquitin-mediated proteolysis; K, celiac toxic; L, opioid; M, immunomodulating; N, neuropeptide; O, contracting; P, antibacterial; Q, stimulated different activities; R, anticancer; S, embryotoxic.

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Concluding Remarks

  1. Top of page
  2. Abstract
  3. Introduction
  4. Cereal Storage Protein Description
  5. Cereal Health Benefits
  6. Cereal Grain Protein Health Benefits
  7. Predicted Biological Activity of Cereal Grain Peptides
  8. Concluding Remarks
  9. References

Cereal storage proteins contain an abundance of potential biological activities, which include peptide sequences with anticancer, antioxidant, antithrombotic, ACE-inhibitor, DPP-IV-inhibitor, and PEP-inhibitor effects. Of the 4 cereal grains evaluated, wheat and barley proteins had the most diversified biological activity and volume of biologically active amino acid sequences. Both also present celiac toxic peptides, while oat and rice proteins did not show much celiac toxic activity. Barley, wheat, and oat had some opioid activity, while only wheat and rice had anticancer peptide sequences. Rice was the only cereal grain to have an RGD sequence. More research is needed on oat and rice storage proteins to understand how they differ from wheat and if their quality and lack of celiac toxic sequences could be beneficial for health and nutrition. Barley and wheat were shown to have the greatest biological peptide potential. Current technology available to release bioactive peptides from food depends on several factors, including method used, bioactive peptide of interest to be released, and intended use of the peptide. Release methods include enzymatic hydrolysis, which utilizes enzymes such as trypsin and pepsin to simulate the environment in the gastrointestinal tract, chemical hydrolysis, which uses acid to break down larger proteins, and fermentation, which releases bioactive peptides after the application of microorganisms to food products (Wang and de Mejia 2005). These methods can also be used in combination to yield desired products, such as in the case of protein hydrolysates in soybean, where enzyme hydrolysis and acid were used together. Heat can be used to release peptides, but there is a higher risk of decreased protein quality. Synthesis is also a viable method, but high costs and the need for specialized equipment impede frequent use. Care should be taken to ensure the peptides released and food-processing methods used do not destroy the bioactivity of the peptides. Finding ways to release the biologically active peptide sequences from these cereal grains, whether during consumption or for nutraceutical use, could be valuable for future applications by the food, nutrition, and pharmacological industries. Although the complete mechanism of absorption and the bioavailability of specific peptides are still under investigation, there is enough evidence to conclude that food bioactive peptides are bioavailable and can be absorbed into the body (Gonzalez de Mejia and others 2012).

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  1. Top of page
  2. Abstract
  3. Introduction
  4. Cereal Storage Protein Description
  5. Cereal Health Benefits
  6. Cereal Grain Protein Health Benefits
  7. Predicted Biological Activity of Cereal Grain Peptides
  8. Concluding Remarks
  9. References
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