Chemistry of camel milk proteins: Chemistry, processing effect, techno-functional & nutritional properties

Introduction

Camels contribute big role in lives of many people particularly which stay in arid or desert area and semi-arid areas of the world and also significant contributors in their ecologies. Camels live in the vast pastoral areas in Africa and Asia and are divided into two different species belonging to the genus Camelus. Dromedary camels (Camelus dromedarius, one humped) that mainly live in the desert areas (arid), and Bactrian camel (Camelus bactrianus, two-humped) which prefer living in the cooler areas. It is a bulky animal that stay in desert with a population of nearly 34 million in that 89% are Camelus dromedaries species and 11% are of Camelus bactrianus (FAOSTAT, 2019) [17] . It contributes 0.36% share of the world's milk production in which Asian countries reported 8% share. In India, camels are mainly highest reported in state of Rajasthan (81.4%) and other states Gujarat (7.6%), Haryana (4.7%), Bihar (2.2%), and Uttar Pradesh (2.0%).

Camel Milk Composition

Camel milk composition has been studied in different parts of the world. The camel milk contains average 3.4% protein, 3.5% fat, 4.4% lactose and 0.79% Ash (Al Kanhal and Hamad) as shown in table 2. It is a noble source of nutrients like protein and vitamin C (3-5 times more compare to bovine milk) in addition to comprising much more therapeutic value when compared to the milk of any other animal species. Camel milk composition varies with breed, geographically, feeding condition (Konuspayeva et al., 2009) [35] . [35]

Camel milk protein

Milk proteins are important bioactive components which provide essential amino acids and are also an energy source. Different technological processing applied in milk sterilization, pasteurization, cheese making are to a large extent determined by the properties of the milk proteins. The milk obtained from camel discrete from bovine milk in composition and structure of its protein components, which influences its functional and biological properties. Camel milk have high nutritional value due their unique components and some are homologous to human milk; thus it can be a good replacement for human milk in cases in which the source of human milk substitute and also good application in infant formula. Camel milk contains high amount of Ig, protective enzymes and insulin like proteins. The unique protein found in camel milk such as peptidoglycan recognition protein, whey acidic protein and lactophorin more in camel milk. In that camel milk proteins has satisfactory balance of essential amino acids which is important aspects of human diet, containing a high amount of β-casein (65% of total casein) and less k-casein and a lack of β-lactoglobulin (El-Agamy, 2009; Hinz et al., 2012; Kappeler et al., 2003) [14,26,33] .

Amino acid profile of camel milk protein

The major amino acid in camel milk is glutamic acid. It has high content proline, leucine, valine and isoleucine which is important cell growth act as branch chained amino acid. The essential: non-essential AA ratio in camel milk, cow milk and human milk are 0.93, 1.0 and 1.07 respectively which is important in human for protein utilization (Zaho et al., 2015) [58] . In camel milk higher amount of sulphur containing amino acid present like methionine, cysteine which are important for working of central nervous system. The ratio of cysteine: methionine is lower in camel milk (0.38) than in cow (0.5) and human (0.6) milk due to the high content of methionine in camel milk proteins. [32,35,61,41] Casein from camel milk The total protein content of camel milk varies from 2.0 to [6,14] . Due to larger diameter leads to poorer aggregation (omar et al.). Casein of Camel milk are more homologous with that of human milk. It contains about five times more hydrolyzed protein β-casein as compared to cow's milk and it is major casein fraction same as human milk. It contain less amount of glycosylate k-casein (3.5%) compare to bovine milk (13%). Higher amount of proline amino acid residues content in camel caseins may lead to destabilization of secondary structures in a more pronounced manner than it does in cow milk caseins (Kappeler, 1998) [32] . The concentration of caseins in camel milk are shown in Table 5. αs 1 -and β-CN of camel milk are phosphorylated to about the same extent as in cow milk, while αs 2 -CN is more heavily phosphorylated (Most hydrophilic) than that of cow milk casein. Molecular properties of camel milk casein shown table 6. [25] Whey protein from camel milk Whey protein is another major fraction of camel milk which reported 0.6-0.8% of total camel milk protein (26-28% of total nitrogen). Camel milk contain unique composition of whey protein components (ElAgamy, 2006; Hinz et al., 2012) [15,26] . It found to be have more unique protein; WAP, PGRP which are absence in bovine as well as human milk. β-lactoglobulin is the major protein allergen which is absent in camel milk (Maqsood et al.,). Due to absence of allergenic whey protein leads to more similarity and quite closer with human milk and helpful for prevention of cow milk allergy. Major whey protein present in camel is αlactalbumin which contains 123 amino acid residues same as bovine α-La and MW 14.6 kDa. It contains more amount of antioxidant rich amino acids residues. Camel milk contains the highest level of IgG (1.64 mg/ml) in that two variant IgG2 and IgG3 which provide additional functionality (Abbs et al., 2013) [1] . Serum albumin in camel milk is higher compare to bovine milk (2.2 g/l). Serum albumin is less susceptible to heat than Serum albumin from bovine or buffalo milk, and it has been demonstrated that denaturing camel Serum albumin at 100 °C for 20 min is equal to heating bovine and buffalo SA at 85 °C for 20 min (El-Agamy, 2000) [13] . [25] Protective protein In camel milk specific proteins that is antibodies or immunoglobulins and non-specific proteins which include lysozyme, Lactoferrin, PGRP and lactoperoxidase.

PGRP (Peptidoglycan recognition protein)

The peptidoglycan recognition protein is an antibiotic protein that is secreted from white blood cell. It has the ability to depolarize bacterial membranes. Inactivation of pathogens occurs by binding to peptidoglycan structures in bacterial cell walls act as pathogen inhibitor for both gram positive and gram negative bacteria; thus the name was given peptidoglycan recognition protein (PGRP). Intracellular component of neutrophils, has been isolated from camel milk. Camel PGRP protein is rich in arginine, but poor in lysine, although the pI (7.94) is highly basic. It presents in camel milk at concentration 110-120 mg/l (Mohamed et al., 2020) [41] . It contain 172 amino acid and 19.1 kDa MW. PGRP concentration reduced during lactation (19%) and increased in the event of severe mastitis by 45% (Kappeler et al., 2004) [30] .

Lysozyme

Camel and Bovine milk both contains trace levels of lysozyme tested, and both have been reported to have a similar molecular weight (MW) of 144 KDa (El-Agamy et al. 2000; Poltronieri et al., 2012) [13,48] . However, the enzyme is not expressed in a healthy lactating mammary gland, and it was not discovered in milk that had no mastitis (Kappeler et al., 2004) [33] . The traces that have been found in camel milk likely came from the blood serum.

Lactophorin

Lactophorin is glycoprotein that reacted to the antisoluble glycoprotein of milk fat globule membrane was purified from the proteose-peptone of whey. It consisted of seven polypeptides with apparent molecular weights 15.442 kDa. It contains 954 mg/l which is second highest whey protein after α-lactalbumin. It is major protein for anti-cancer activities as well as inhibition of lipase (Ibrahim et al.).

Lactoferrin

Lactoferrin is glycoprotein and iron binding protein which protect over bodies again bacterial action giving bacteriostatic and bactericidal effect. Camel lactoferrin has 91.6% sequence similarity with bovine or human lactoferrin.

It contained a higher level (0.22 mg/ml) of lactoferrin compared to the other species except humans. Camel lactoferrin has 689 amino acid residues, a molecular weight of 75.3 kDa, and an isoelectric point of pH 8.63. Camel Lactoferrin has been discovered to simultaneously perform the two essential tasks of iron scavenging (lactoferrin) and iron release (transferrin). Antimicrobial activity against the Gram-negative bacterium E. coli is higher than for other orthologues.

Lactoperoxidase

Lactoperoxidase is oxidoreductase enzyme which generally found in saliva, tears and milk. It contributes non immune host defense system provide bactericidal effect against gram negative bacteria. Lactoperoxidase system in which hydrogen peroxide (H 2 O 2 ) is reduced, and a halide, for example, iodide (I-) or bromide (Br-) for example, thiocyanate (SCN -), is subsequently oxidized (Ferrari et al., 1997) by produced compound OSCN -and OHSCN generating free SH groups in cytoplasmic membrane through it gives antimicrobial activities especially gram negative bacteria. Natural substrates of lactoperoxidase in milk are thiocyanate and iodide, of which milk contains trace amounts. Camel milk lactoperoxidase is a monomeric protein, which has 79.3% sequence similarity to human myeloperoxidase and 79.2% sequence similarity to human eosinophil peroxidase. The isoelectric point of camel lactoperoxidase was 8.63, whereas in bovine milk it was found pH 7.90 (Dull et al., 1990) [10] . LP has 611 amino acids and 69.3 kDa MW. Camel LP enzyme even more heat stable than the ruminant variants.

Insulin

Camel milk is considered best choice for overcoming pathophysiologic complications and in providing the beneficial nutritional treatment especially for diabetes patients. Insulin is small protein or peptides hormone which regulate blood glucose level. It contain four times higher insulin (52 unit/liter) than bovine milk. Camel milk Insulin is lower MW comparable to insulin which mimics interaction of insulin with their receptors. It is packaged in nanoparticles smaller in size that allow it to pass easily through stomach and allows its entry to circulatory system act proper blood sugar regulation. It also inhibits the elevation of hormones, TNF-α and TGF-β1 levels which are produced in response to Diabetes. Whey protein in camel milk act as anti-oxidant which help in healing process reduce during diabetes (Aqib et al., 2019) [3] . Effect of different processing on camel milk protein Different studies showed processing of camel milk is difficult compare to bovine milk mainly due compositional difference related to protein. Camel milk observed to be have poorer heat stability as well coagulation properties which directly affect product manufacturing. Properties of the milk proteins most influences or affected by technologically process including pasteurisation, sterilisation, fermentation, and cheese making. In all processes, heating is mainly used for preservation of camel milk and its products which affect the protein stability mainly affects its structure.

Heating

Heat treatment is an integral part of the dairy processing industry as it is essential for destroying spoilage and pathogenic microorganisms, extending the milk's shelf-life, and ensuring its safety for human consumption (Felfoul et al., 2016; Yirda, Eshetu, & Babege, 2020) [19,57] . Different process used mainly low heat and high heat treatment given e.g., Pasteurization, UHT, Sterilization etc. In camel milk alkaline phosphatase enzyme inactive at higher temperature compare with bovine milk so its not used as a indicator to check the efficiency pasteurization. γ-glutamyl transferase (GGT) is used as a potential indicator for a proper pasteurization process of camel milk because it is destroyed between 10 to 20 minutes at 72 °C (Wernery, 2007) [55] .

Heating effect on protein

Heat treatments affect the protein stability and functional properties of milk. As increase in temperature causes denaturation of whey proteins which leads to flocculation, protein sedimentation, gelation and aggregation with other unfolded monomer protein. (Tolkach & Kulozik, 2007) [54] . It is unstable at heating temperature of 120 °C to 130 °C at all pH values (6.5-7.1) and coagulated in 2-3 min compare to 40 min in bovine milk.

Effect on whey protein

This process particularly affects the protein which contributes denaturation of protein. Whey proteins from camel are more heat resistant than bovine milk proteins in order of α-lactalbumin > β-lactoglobulin > serum albumin. The degree of denaturation for camel milk whey proteins observed to be 32 to 35% at 80 °C and 47 to 53% at 90 °C versus 70 to 75% at 80 °C and 69% denaturation of IgG (Alhaj et al.,). During heating changes occur in protein structure (unfolding) identified heated milk at 63 °C ranged from 15%-61% and at 98 °C from 79%-98% (Benabdelkamel et al., 2017) [5] . Camel whey protein mainly has more stability in presence of metaloprotein which provide structure stability. On Heating at 90 °C/5min; 67% of camel milk α-lactalbumin remained intact compared with only 5% of a-lactalbumin in bovine milk. Felfoul et al. (2017) [20] reported that heating camel milk at 80 °C for 60 min induced a complete destruction of α-la and PGRP and a decrease of 42% of serum albumin concentration.

Effect on casein

Camel milk caseins are less stable than bovine milk caseins at higher temperatures due to variation in protein molecular properties (less k-casein). Camel milk k-casein is highly liable to heat as it is depleted at temperatures above 100 °C due exposure to internally buried amino-acid residues. Camel milk α S -casein and β-casein are also affected by high heating temperatures but they are more stable than k-casein (Clement, 2018) [8] . Largely heating effect on hydrophobicity of camel β-casein. Heat-treated camel βcasein was found to possess greater abilities to form softer emulsions under acidic conditions (Ellouze et al., 2021) [16] .

Protective protein

Heating of camel milk at 65 °C/30 min has no significant effect on lysozymes and lactoferrins; however, a significant loss occurs in IgG activity. The activity of IgG in camel milk observed to be 69% where in cow and buffalo it completely lost activities at 75 °C/30. Lactoferrin lost 58% their activity at 85 °C for 30 minutes. Protective proteins, the order of heat resistance found was lysozyme > lactoferrin > IgG.

Camel milk has the poorer heat stability, due to:

a) The lesser amount of κ-casein and the lack of βlactoglobulin (Kappeler, 1998) [32] , which are important in milk stabilization. b) The salt balance (ratio of Ca and Mg: citrate and phosphate) due to citrate level in camel milk is lower than that in cow milk (El-Agamy, 2000; Farah and Ruegg, 1989) [13,18] .

Coagulation

The coagulation of milk proteins depends upon the type of coagulant as well as the nature and composition of casein. Different coagulants such as proteolytic enzymes, acid have been used for milk coagulation during manufacturing of cheese. In cheese mainly use proteolytic enzyme derived from animal, plant, microbial sources. Manufacturing of cheese is challenging. RCT of camel milk cheese is two to four time higher compare to bovine milk cheese (Ayush et al., 2022) [41] . Enzymatic coagulation of milk by proteolytic enzymes occur in mainly in two steps. κ-CN prevents micelle aggregation by steric hindrance and charge repulsion. In first step is characterized by hydrolysis of κ-CN in that Cterminal part is specifically cleaved during the enzymatic reaction at a hydrophobic cleavage site, which is Phe105-Met106 in cow κ-CN. In the second step of the renneting process, an exponential increase in coagulation of casein micelles is found. Aggregation starts when 60-80% of κ-CN is cleaved. The reduction of pH and addition of Ca++ increases curd firmness (Dalgleish, 1992) [9] . In camel milk action of chymosin differ it selectively cleaves at the Phe

Reason for weak coagulation

The low concentration of k-casein in the milk and the larger casein micelles size have been primarily reason for the softness of camel milk cheeses. Low κ-casein: β-casein ratio (≈0.05 in camel milk vs. ≈0.33 in Bovine milk). Large casein micelles (260-300 nm) with reduced surface area has been associated with increased RCT which reduced cheese curd firmness and lower the overall quality of cheese (Glathz et al., 2010) [23] . Other remarkable difference between Camel milk and bovine milk whey proteins is that Camel milk lacks β-lg which has important implications on milk functional properties mainly through its heat-induced association with κ-casein. More amount of protective proteins, e.g., lysozyme, lactoferrin, and lactoperoxidase have antimicrobial properties and have been speculated to slow bacterial growth in camel milk (El Sayed et al.,1992) [12] .

Improved cheese coagulation and gelling properties

Hattem et al. found a synergistic impact between the addition of CaCl 2 up to 20 mg/100 ml of camel milk and thermal treatment of camel milk in lowering RCT using bovine chymosin. Different method are used for improving camel milk cheese gel strength. Using HPP process (200-400 MPa) mixture of different species milk as well as using microbial enzyme such that microbial transglutamase (cross linking enzyme) improve coagulation properties as well as reduced RCT time (Mbye1 et al.) Recombinant camel chymosin production which is derived from gene in a strain of Aspergillus niger now also used.

Ultrasonication

Ultrasonication is an emerging nonthermal preservation technology for the processing of dairy products that is widely used owing to its low cost and ease of operation. It affect tertiary and quaternary structures of proteins, which facilitates accessibility of enzymes for hydrolysis of proteins and release of peptides (Ozuna et al., 2015.) [46] Improve the release of bioactive peptides. Increased antioxidant and angiotensin converting enzyme inhibitory activities.

Techno-functional properties of camel milk protein

Functional properties are those qualities or characteristics excluding nutrition, that determine their satisfactory use in food products. These characteristics could include mouthfeel, viscosity, structure and appearance. Milk proteins influence functionality that provide desirable textural or other attributes changes to the finished product.

In techno functional properties include solubility, gelling, foaming and emulsification. Camel milk protein is less soluble than bovine milk protein.

Foaming

Foams are most commonly formed by mechanically dispersing air into a solution containing surface-active agents. Colloidal systems where air bubbles created are stabilized by a matrix composed of surface active agents of milk (i.e., protein). Camel milk protein have better foaming capacity compare to bovine milk due presence of higher amount of β-casein (Hailu et al., 2016) [25] . It is also rather surface active as a result of its amphipathic nature and plasmin hydrolysed bovine β-casein has shown improved foam forming and stabilising properties compared to its intact form (Caessens et al. 1997) [7] . Laleye et al. (2008) [38] reported that camel milk whey can form stable foams at pH 7 which useful for food formulation. Better foaming capacity values (~138%) of camel milk than bovine milk (~115%) at 20 °C.

Emulsification

Emulsification is heterogeneous systems formed by dispersing one or more phases in a continuous phase and they can be stabilized by incorporating surface-active agents. It mainly related oil-water interface. Due to more amount of β-casein amphilic nature attributes higher emulsification capacity (Esmaili et al.).

Gelling

The gelling properties of whey proteins are due to unfolding and denaturation followed by aggregation (Foegeding et al., 2002) [22] . Protein-protein & protein-water interactions are balanced that 3-D network or gel was formed. In camel milk due to absence of β-lactoglobulin and less amount of kcasein weak gel form mainly related β -lg and k-casein interaction and form weak gel. Functionality improved using hydrolysis process. Camel milk protein hydrolysates reported higher techno-functional properties compare to unhydrolyzed camel milk proteins. Enzymatic hydrolysis of protein release peptides with lower MW, different hydrophobicity and solubility properties, and a greater number of ionisable groups which improves the functionality. Endo-peptidase enzymes hydrolyze proteins rapidly, which reduces the amount of free amino acids for improved bioavailability (Foegeding et al. 2002) [22] . Camel milk protein highly degraded by pepsin; resistant to chymotrypsin & trypsin (Saliha et al; Shamsi et al.). Other than enzymatic hydrolysis by using fermentation derived bioactive peptide also improve functionality such as ACE inhibitory and antioxidant activities. Camel milk peptides have higher bioavailability due more hydrolysis of protein presence of β-casein.

Nutritional and therapeutic properties of camel milk

Camel milk become new emerging super food aspect related to medicinal as well as therapeutical value. Camel milk has high nutritional value and has many components and properties homologous to human milk; thus, it can be a good replacement for human milk. In that main camel milk protein seek more attention due to uniqueness and functionality. It have the satisfactory quality balance of essential amino acids as well as ratio of essential amino acid and nonessential amino acid ratio for human diets for proper protein utilization. Nowadays camel milk has potential use related to serve disease including diabetes, Autism, allergies (Kumar, 2015). IGs of camel milk protein function in the treatment of complex developmental neurological disorder (Autism). It have better digestibility compare to bovine milk due higher whey protein to casein ratio or lower casein to whey protein ratio (76:24). [50] which mainly related to protein especially major protein. In alternative of that camel milk which contribute importance source reduce allergy or making less allergenic due absence of major allergen β-lg (Merin et al., 2001) [39] and presence of immunoglobulin. Antiallergenic property of Camel milk also is due to the similar protein profile to human mother's milk in lacking βlg and higher proportion of α-lactalbumin (Mojtahedi, Izadi, Seirafi, Khedmat, & Tavakolizadeh, 2018) [42] .

Antioxidative properties

Reactive oxygen species is an aspect of oxidative stress which are associated with many diseases such as rheumatoid arthritis, diabetes, inflammation, atherosclerosis and cancers. Thus, the need for naturally occurring antioxidants prevention against free radical generation. In camel milk protein main Lactoferrins (LF) which improve antioxidant ability by scavenging free radicals; also give antiaging properties other than camel milk protein higher αlactalbumin which rich in antioxidant amino acid (Salami et al., 2009) [51] . Bioactive peptides with lower molecular weights pauses antioxidant activity. Purified and identified two novel peptides (NV-13 and KQ-15) from camel milk proteins and examined antioxidant properties of these peptides (Homayouni-Tabrizi et al., 2016) [28] .

Antidiabetic properties

Diabetes is a group of metabolic disorders associated with chronic hyperglycemia in the blood due to a work in insulin secretion, insulin function. Primary treatment for type 1 diabetes is insulin, camel's milk plays a vital role in maintaining the pancreatic β-cell's function. It improves obesity, inflammation, wound healing and oxidative stress damages as diabetes complications (Agrawal et al., 2013). Camel milk may prepare about 60% of the insulin in diabetic patients (Shori et al., 2015) [52] . Hormones like glucagon and glucose-dependent insulinotropic polypeptides, such as gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP1), as well as enzymes such as the endoprotease dipeptidyl peptidase IV (DPP-IV) and its proteolytic effects on GIP and GLP-1, have a crucial role in the control of insulin synthesis and secretion by the pancreases (Ayoub et al., 2018) [4] . [49] ACE inhibitory properties Camel milk derived Bioactive peptides from camel milk has ACE inhibitory activity. Ile-Pro-Pro liberated during GI digestion of camel milk κ-casein which has hypotensive effect. Proline amino acid in structure of formed peptides has significant role in lowering of blood pressure. Tripeptides Val-Pro-Pro & Ile-Pro-Pro which are inhibitors of angiotensin converting enzyme properties of peptides that regulate blood pressure (Dziuba B., & Dziuba, 2014) [11] .

Autism

Autism spectrum neurological disorder is of behavioral symptoms in affected children distinguished by emotional confusion, symbolic behavior, difficulties with social interactions & verbal and nonverbal conversations. Ig and lactoferrin of camel milk protein function in the treatment of this complex developmental disorder. Decrease of Autism symptoms in children aged 5-14 years by regular 14 day consumption of pasteurized camel milk (0.5 l/d) (Ozkaya, 2013) [45] . Main in autism related oxidative stress which reduce camel milk protein. Effect of camel milk supplementation on oxidative stress biomarkers such as myeloperoxidase, superoxide dismutase (SOD), and glutathione in children with autism.

Antimicrobial properties

Camel milk contains protective proteins like Igs and LF. Isolated LF from camel milk through the disruption of cell membrane had the maximum antibacterial activity against this food-borne pathogen. Peptides generated by enzymatic digestion of LF have an antimicrobial potential (Abbas et al. 2013) [1] . The highest activity against E. coli O157:H7 compared to LFs isolated from other milk (Conesa et al,). Anticancer activities: Camel milk inhibited both human hepatoma and breast cancer cell survival and proliferation through the activation of both the extrinsic and intrinsic apoptotic pathways (Korashy et al., 2012) [36] . Antitumor fraction from whey proteins of camel milk which have eradicate epithelial cell lines of human esophageal carcinoma (Nakamura et al., 2013) [43] . Antitumor fraction from whey proteins (LF) of camel milk which was able to eradicate the epithelial cell lines of human esophageal carcinoma (khan et al., 2021) [34] . Interaction of oleic acid and hydrophobic core of α-lactalbumin in a molten globule state which improve the apoptotic activity to eradicate selective tumour cells (Yang et al., 2018) [56] .

Conclusion

Camel milk is rich in health-beneficial substances with novel protein which contribute functionality as well therapeutical potential. The composition and molecular properties of camel milk protein is different from bovine milk and similarity with human milk due absence of β-lg and contains more protective proteins. In techno-functional properties it has better foaming as well as emulsification capacity compare to bovine milk due to presence of more amount of β-casein. Camel milk whey protein are more stable compare to bovine milk. It has produced weak gel during coagulation. Camel milk is considered an invaluable alternative source to cow milk. It has much less allergic effects than cow. Camel milk is an excellent candidate to improve the growth performance of infants and children. Camel milk has comparatively higher functional contribution to human health as a result of the unique composition of caseins and whey proteins (WAP, α-la, LF, PGRP-S, and IgG with the different variants of Ig).

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