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Rationale

 

The production of natural ACE inhibitors using bioactive peptides from meat waste wasn't our initial idea to start with. As food innovators, we each wanted to produce something relating to food in some context but also something which would benefit the health of the public. There were three main ideas which resulted from our group brain storming sessions at the start of this project which were as follows:

 

  • Using bioactive compounds from fruit & veg for treating diseases.

  • Utilizing nutrients from food waste for generation of nutraceutical vitamin drink.

  • Possible production of cyclosporine from new fungi.

 

Each group member carried out some in-depth research on their proposed ideas to see if there were any gaps in the industry for such products or if there was a want/ need for such products. This would essentially dictate which idea had the most potential which we came together to discuss in a group meeting the following week. Cyclosporine is currently used therapeutically to prevent organ rejection following transplants, therefore it was concluded from the group discussion that the areas surrounding food waste & bioactive compounds were the most promising but why? This is because valuable food is wasted each year. To be precise, in 2016 it was determined that approximately 88 tonnes of food is wasted yearly, amounting to an estimation of 143 billion euros (Browne, 2017). At present, approximately 42% of food waste is produced by households, 39% results from the food industry, 5% results from distribution while a further 14% is produced from food service sectors e.g. restaurants and catering (Fig. 1). By 2020 it is predicted that the levels of food waste is to rise to an astonishing 126 million tonnes if no action is taken to address this ongoing problem (Kumar, Yadav, Kumar, Vyas, & Dhaliwal, 2017). Waste in general has been an immense problem for years and continues to be so. In recent times there has been increasing interest in more efficient ways to manage food waste & utilize its resources into functional products as the amount of food waste produced from industrial, household & agricultural activities is continually rising.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

It was further recognized from online research that plant and animal-derived wastes still contain bioactive compounds such as phenols, phytochemicals, carotenoids, sterols etc. even after processing. These are known to benefit human health and reduce the risk associated with several diseases. Therefore the conclusion was drawn that food waste holds excellent potential for the production of nutraceutical products due to the abundant presence of bioactive compounds.

 

 

Figure 1. Pie chart summarizing the main activities producing the most food waste.

Where did the idea stem from?

Why this Product?

Although there is an abundance of different bioactive compounds which stem from various types of food waste, the team decided to solely focus on the production of bioactive peptides from meat waste for application as natural ACE inhibitors to treat hypertension. There are several reasons contributing to this decision. Primarily, the goal was to create a novel, innovative idea which would benefit food industries as well as the public health. There has already been an extensive amount of research already done in the general area of bioactive compounds and their potential in treating disease. However, only a limited number of studies exist relating to the isolation of bioactive peptides from food waste proteins and their potential as biologically active compounds for application as medicinally important products. Within this context, previous reports have mainly just looked at sourcing bioactive peptides from gelatin, plant sources, milk and other dairy products. Therefore we opted to take an alternative approach and look at meat waste as our main resource for these bioactive peptides. In comparison to the different types of food waste existent i.e. veg, fruit, meat, seeds, citrus, dairy, cereal and crops, waste by-products from meat are amongst the richest sources of proteins (Lafarga & Hayes, 2014). By reusing meat waste for the generation of bioactive peptides for application as natural ACE inhibitors, our product  will in turn offer the following benefits:

 

  • Increase waste value.

  • Improve waste management.

  • Financially benefit the meat industry.

  • Decrease the burden of environmental & economical problems associated with the disposal of meat waste.

  • Decrease the burden associated with the use of chemicals in drugs.

  • Benefit the health of patients suffering from hypertension.

About Hypertension

The principal rationale behind our decision to generate bioactive peptides as an alternative aid for hypertension is due to the prevalence of high blood pressure in modern society. It is also a condition that is inherently personal to one of the group members as issues with heart disease and hypertension is evident amongst the family history. Heart disease and hypertensive issues are attributable to hereditary sources, even in the most healthy and active people. Several members of the family have suffered near-death heart attacks and battle with extremely high blood pressure on a daily basis, despite taking medication and living a very healthy lifestyle. Before launching into the infinite details, we need to have a good understanding of the disease we aim to treat.

 

 

Statistics on Hypertension

 

“High blood pressure (or hypertension) is when blood pressure, the force of the blood flowing through your blood vessels, is consistently too high" (American Heart Association, 2017). About 85 million Americans – that’s 1 in every 3 adults over the age of 20 have high blood pressure and 1 out of every 6 don’t even know they have it. In the most recent TILDA (The Irish Longitudinal on Ageing in Ireland) study in 2015 which carried out research monitoring the prevalence of high blood pressure in adults over the age of 50 in Ireland, it was found that 45% of older adults had high blood pressure but weren’t aware of it. This lack of awareness was particularly more common in the male population tested and amongst the youngest age group examined which were adults aged between 50-64 years. This study further revealed that 64% of the over 50’s in Ireland have high blood pressure, but only 59% of those were found to be taking regular medication to treat this disease (C.M. Murphy et al., 2016). At present, there are five main types of blood pressure ranges identified and they are normal blood pressure, prehypertension which is known as the early stages of hypertension, stage 1 hypertension, stage 2 hypertension and hypertensive crisis. The blood pressure ranges for each category are summarised below in table 1. Our blood pressure is represented by two main numbers, there is the systolic blood pressure which is the upper number that is representative of our blood pressure when our heart beats and the diastolic blood pressure (the lower number) which is indicative of our blood pressure level while our heart rests between beats (American Heart Association, 2017). The level of the systolic blood pressure tends to be of more importance.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

What damage does hypertension do if untreated?

 

High blood pressure can be present for years before any symptoms become obvious. It is also known as a silent killer. It is the main cause of deaths in both Irish men and women. When hypertension is left untreated it can lead to disease, a disability, poor quality of life or even a heart attack and death. Approximately 1/3 of those with untreated hypertension die of heart disease related to poor flow to the heart – also called ischemic heart disease. A further 1/3 die of stroke. However, treatment as well as a good lifestyle including healthy eating and exercise can eliminate the risk of complications (Mayo Clinic, 2016). The main damage induced by prolonged hypertension include:

 

  • Damage to arteries - Undamaged, healthy arteries are strong and elastic and have a smooth inner layer allowing blood and the nutrients it contains to reach all parts of the body without obstruction. However, hypertension raises the pressure within the vessels to increase, initiating damage to the vessels which will eventually lead to heart disease and other illnesses if left untreated. Eventually, this increased pressure within the vessels enter the blood stream, they get caught in the tears (Mayo Clinic, 2016). This leads to hardening of the blood vessels, which in turn limits the blood flow to the rest of the body arteries causing the smooth cells within the vessel to get damaged. When fat from the diet enters the blood stream, they get caught in the tears. This leads to hardening of the blood vessels, which in turn limits the blood flow to the rest of the body.

 

  •  Aneurysm - Over a long period and without treatment, the constant high pressure through an artery can cause a weakening in the wall leading to a bulge (aneurysm). An aneurysm can rupture at any time causing severe internal bleeding which is a life-threatening scenario. Aneurysms can occur in any artery throughout the body but are most common in the aorta.

 

  • Coronary artery disease - Coronary artery disease affects the blood vessels which pump blood to the heart muscle. Arteries get narrowed as a result of coronary artery disease and don’t allow the blood to flow as easily to the heart. This can lead to chest pain, irregular heart beat (arrhythmia) and heart attack.

 

       Other types of damage which may occur but are less common are summarized below in table 2.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2. Summary of additional damage which may result from hypertension

Table 1. Summary of blood pressure ranges of the different stages of hypertension (American Heart Association, 2017)

It was also of great importance to grasp the idea of how current synthetic ACE inhibitors work so a similar concept could be adapted with the natural ACE inhibitors. In our bodies the rennin- anginotensin system is responsible for regulating the systemic blood pressure, the rate of glomerular filtration and renal blood flow in our bodies. When our blood pressure drops below the ideal (<90mm Hg systolic or <60mm Hg diastolic), otherwise known as low blood pressure or hypotension, baroreceptors in the blood vessels detect this change and triggers the juxtaglomerular cells in the kidneys to release the enzyme renin which cleaves and converts angiotensinogen (precursor protein manufactured in the liver) and breaks it down to form angiotensin I (precursor hormone). In the lungs a membrane bound dipeptidase enzyme called angiotensin – converting enzyme (ACE) then catalyzes the conversion of angiotensin I into angiotensin II - an active hormone also referred to as a ‘vasoconstricitve’ hormone. This hormone essentially causes the constriction of the blood vessels and in turn increases the blood pressure in the body thus resulting in hypertension which is one of the major risk factors of cardiovascular disease. Angiotensin II also has additional effects on the body including triggering an increase in the rate of renal blood flow and glomerular filtration rate (Cheprasov, 2016).

 

To treat patients suffering from hypertension induced by angiotensin II, synthetic ACE inhibitors have been created which are a group of synthetic drugs that prevent the body from creating the active hormone. Current ACE drugs on the market include benazepril, captopril, enalapril, fosinopril, Lisinopril, moexipril, quinapril and Ramipril – each which differ in their efficiency and duration of action (Klabunde, 2010). They work by blocking the angiotensin – converting enzyme in the lungs thereby inhibiting the conversion of angiotensin I into angiotensin II (Fig. 2) (Ryder, Bekhit, McConnell, & Carne, 2016). By inhibiting the formation of angiotensin II, ACE inhibitors cause dilation of the blood vessels thereby allowing the ease of flow of blood and reduction in blood pressure. Despite their efficiency in lowering blood pressure there are a number of negative side effects associated with these synthetic drugs including: a persistent dry cough, dizziness, tiredness, weakness, rash and headaches. On rare occasions, ACE inhibitors may also trigger allergic reactions causing swelling around the mouth and face (Klabunde, 2010). The negative impact these drugs may have on patients has recently prompted scientists to look for more natural ACE inhibitors that can be used in replacement of their synthetic counterpart that are free from such side effects which is essentially the underlying concept of our product.

Synthetic ACE inhibitors

Figure 2. Mechanism of action of ACE inhibitors (Gandhi, 2016)

So what are bioactive peptides? 

Bioactive peptides are natural compounds deriving from food which typically have a peptide chain composed of between 2-20 amino acids. These compounds may exist in two main forms - either encrypted or latent form. Encrypted form is when they are inactive, while in their latent form means they are existent within a parent protein yet they aren't active until being released by hydrolysis. Hydrolysis is a process that essentially breaks down the parent protein into its amino acid constituents and activating the biologically active peptides for use as functional components (Ryan, Ross, Bolton, Fitzgerald, & Stanton, 2011). It seems as though peptides which exert antihypertensive properties are typically short in length and found to be between 2 - 12 amino acids long (Lemes, et al., 2016). Bioactive peptides have been shown to possess several physiological functions which are summarized below in figure 3.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Out of the functions outlined in figure 3 above, our team’s attention is focused on the bioactive peptides with antihypertensive properties. These particular peptides are reportedly capable of preventing the action of angiotensin-converting enzyme by both competitive and non-competitive mechanisms. Competitive inhibition is accomplished by the peptides interacting with the ACE enzymes active site thus preventing substrate binding. They may also non-competitively block the enzyme from action by binding to the ACE enzyme itself and altering its shape preventing binding of the substrate to the active site (fig. 4). In ACE inhibitory bioactive peptides, their antihypertensive capabilities have been continuously linked to the presence of the hydrophobic amino acid proline at the C- terminal end/ branched amino acids such as isoleucine & valine or else positively charged amino acids at the terminal position e.g. lysine and arginine (Lemes, et al., 2016).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

There are three main classes of ACE inhibitor type peptides which derive from food sources:

 

  1. True inhibitor type - which are peptides that remain unaffected following preincubation with angiotensin – converting enzyme.

  2. Substrate type - are peptides which tend to be subjected to hydrolyzation when they encounter the ACE enzyme.

  3. Pro-drug type - are peptides which when they encounter the ACE enzyme or proteases within the digestive tract, they are converted into true inhibitor type peptides.

 

Both true inhibitor type and pro drug type peptides are deemed as most suited for reducing hypertension as they have displayed good inhibitory activity in in vivo studies mainly because they are more stable and will therefore reach the site of action without their inhibitory activities being diminished as much ( Ryan, et al., 2011). These type of peptides are widely found within meat sources which is another feature that steered us towards using meat waste as our main source for recovering biologically active peptides.

Figure 3. Flow chart of the known properties of bioactive peptides derived from food proteins.

Figure 4. Schematic of inhibition mechanisms of bioactive peptide ACE inhibitors (TutorVista, 2016).

Waste in the meat industry 

Additionally, the team decided to use meat waste for recovering bioactive peptides because the majority of the animals slaughtered are discarded as waste by being sent for incineration, rendering or to landfills meaning great amounts of compounds with potential in medicinal applications are just being lost. According to the Agriculture and Consumer Protection (2017), a cow for example - referred to as “steer” when sent for slaughter, has a carcass weight of 272 - 318kg. As displayed by Jayathilakan et al. (2012), for a steer there is 83kg of solid waste generated from bovine meat per cow. For each cow slaughtered, 26% of that cow is going to waste. Pigs and goats generate smaller amounts of waste at 2.3kg and 2.5kg respectively. These figures are astonishing, yet for the project at hand it is quite useful. Once that cow has given its life, it is best to ensure that the meat obtained is being fully used, therefore the cow did not die to merely become a juicy steak. It is imperative that each and every morsel of the being is utilized to its greatest extent which is what we are striving towards. Furthermore, the proper disposal of meat waste can be difficult posing environmental & economical problems and it is also expensive to discard of due to the biological nature of meat (Lafarga & Hayes, 2014). It is susceptible to pathogenicity due to its high level of enzyme, high water content and its affinity for auto-oxidation. These current challenges being experienced by the meat industry are other reasons why we chose to reuse meat waste for production of medicinally important products as it is a more cost-effective approach than the typical methods of disposal and will also help minimise the present issues.

 

 

Types of meat waste and their uses

 

As defined by the European Union in Regulation (EC) No 853/2004, meat is "the edible parts removed from the carcass of domestic animals including bovine, porcine, ovine and caprine animals, poultry and wild game". Meat differs from its by-products or waste in other words as these are classed as "the entire bodies or parts of animals, products of animal origin or other products obtained from animals, which can, but are not intended for direct human consumption" (European Union, 2014). The bulk of meat waste is obtained through processing stages, primarily in slaughterhouses, fish processing plants and butcher shops. At this point in time, meat waste is typically used in animal feed, fertilizer, some cosmetics or processed into by-product ingredients for the food industry while the remainder is discarded of. The types of waste arising from domestic animals that aren’t permitted to be sold directly for human consumption as meat or used in meat products include bones, internal organs, tendons, fatty tissues, skin, blood and contents of the gastro - intestinal tract which all interestingly are valuable from a bioactive peptide generation point of view as they are rich in protein (fig 5.). There is such a high quality and quantity of nutritive value of these meat by-products, with the organs & muscle being the most enriched in comparison to ears, feet, tails and surprisingly, the liver. Bioactive peptides are throughout all protein-enriched elements of such animals. For this project the meat substrate of focus will be the organs, muscle and tissue of the animal, as opposed to the ears, feet and tails as they are mainly composed of collagen and fattier substances. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 5. Flow chart of the current uses of different types of meat waste & by-products and their potential uses for generation of bioactive peptides (Lafarga & Hayes, 2014)

References

Agriculture and Consumer Protection (2017) Meat cutting and utilization of meat cuts. Guidelines for slaughtering meat cutting and further processing. Retrieved 17th October 2017, from http://www.fao.org/docrep/004/T0279E/T0279E05.htm.

 

American Heart Association. (2017, October). The Facts About High Blood Pressure. Retrieved October 8, 2017, from American Heart Association: https://www.heart.org/HEARTORG/Conditions/HighBloodPressure/GettheFactsAboutHighBloodPressure/The-Facts-About-High-Blood-Pressure_UCM_002050_Article.jsp

 

Browne, N. (2017, May). Irish food waste ‘contributes to €143 billion bill’. Retrieved October 25, 2017, from Agriland: http://www.agriland.ie/farming-news/irish-food-waste-contributes-to-e143bn-bill/

 

Cheprasov, A. (2016). Renin Angiotensin Aldosterone System (RAAS): Pathway, Functions & Terms. Retrieved October 16, 2017, from Study.com: http://study.com/academy/lesson/renin-angiotensin-aldosterone-system-raas-pathway-functions-terms.html

 

Daliri, E.-M., Oh, D., & Lee, B. (2017, April). Bioactive Peptides. (M. Hayes, Ed.) Foods, 6(32), 1-21.

Gandhi, M. (2016, May). ACE. Retrieved October 16, 2017, from LinkedIn Slideshare: https://www.slideshare.net/Cology/ace-61730852

 

European Commission (2016), Food Waste. Food. Retrieved on 15th October 2017, from https://ec.europa.eu/food/safety/food_waste_en.

 

European Union. (2004, April 30). Corrigendum to Regulation (EC) No 853/2004 of the European Parliament and of the Council of 29 April 2004 laying down specific hygiene rules for food of animal origin. Official Journal of the European Union, 226, 22-82. Retrieved from https://www.fsai.ie/uploadedFiles/Reg853_2004(1).pdf

 

European Union. (2014, January 1). Regulation (EC) No 1069/2009 of the European Parliament and of the Council of 21 October 2009 laying down health rules as regards animal by-products and derived products not intended for human consumption and repealing Regulation (EC) No 1774/2002 (Animal by-products Regulation). Retrieved October 30, 2017, from EU Law and Publications: https://publications.europa.eu/en/publication-detail/-/publication/bdb425ef-1cd9-4051-bf11-7461132a4564/language-en

 

Inner West Council. (2013). Food Waste Recycling. Retrieved October 27, 2017, from Inner West Council Leichhardt: http://www.leichhardt.nsw.gov.au/Living-Here/Waste-and-Recycling/Waste-and-Recycling/Food-Waste-Recycling


Jayathilakan, K., Sultana, K., Radhakrishna, K., Bawa, A.S. (2012) Utilization of byproducts and waste materials from meat, poultry and fish processing industries: a review. Journal of Food Science and Technology, 49 (3), 278 - 293.

 

Klabunde, R. (2010, March). Angiotensin Converting Enzyme (ACE) Inhibitors. Retrieved October 10, 2017, from Cardiovascular Pharmacology Concepts: http://cvpharmacology.com/vasodilator/ACE

 

Kumar, K., Yadav, A., Kumar, V., Vyas, P., & Dhaliwal, H. (2017). Food waste: a potential bioresource for extraction of nutraceuticals and bioactive compounds. Bioresources and Bioprocessing, 4(18).

 

Lafarga, T., & Hayes, M. (2014). Bioactive peptides from meat muscle and by-products: generation, functionality and application as functional ingredients. Meat Science, 98, 227-239.

 

Lemes, A., Sala, L., Ores, J., Braga, A., Egea, M., & Fernandes, K. (2016, June). A Review of the Latest Advances in Encrypted Bioactive Peptides from Protein-Rich Waste. International Journal of Molecular Sciences, 17(950), 1-24.

 

Mayo Clinic. (2016, November 23). High blood pressure dangers: Hypertension's effects on your body. Retrieved October 8, 2017, from Mayo Clinic: https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/high-blood-pressure/art-20045868?pg=1

 

Murphy, C. M., Kearney, P. M., Shelley, E., Fahey, T., Dooley, C., & Kenny, R. (2016, October 17). Hypertension prevalence, awareness, treatment and control in the over 50s in Ireland: evidence from The Irish Longitudinal Study on Ageing. Journal of Public Health, 38(3), 450 - 458.

 

Ryan, J., Ross, R., Bolton, D., Fitzgerald, G., & Stanton, C. (2011, August). Bioactive Peptides from Muscle Sources: Meat and Fish. Nutrients, 3, 765-791.

 

Ryder, K., Bekhit, A.-D., McConnell, M., & Carne, A. (2016). Towards generation of bioactive peptides from meat industry waste proteins: Generation of peptides using commercial microbial proteases. Food Chemistry, 208, 42-50.

 

TutorVista. (2016). Enzyme Kinetics. Retrieved from TutorVista.com: http://chemistry.tutorvista.com/biochemistry/enzyme-kinetics.html

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