Beta casein proteins – A comparison between caprine and bovine milk

Bovine milk is regarded as nature's perfect food due to presence of vital nutrients. However some peptides are generated after proteolytic digestion of β-casein that have opioid properties and may increase the risk of chronic diseases. There are 13 genetic variants of bovine beta-casein; out of these A1 and A2 are the most common in dairy cattle breeds. The A1 and A2 variants differ only at position 67, which is histidine in A1 or proline in A2 milk. Earlier published reports have indicated that A1 β casein could be responsible for several health disorders like diabetes, coronary heart disease etc. while A2 β-casein is generally considered safe for human consumption. In the present study, an effort was made to sequence characterize β casein gene and identify allelic distribution of A1A2 alleles in native cattle of Ladakh region adapted to high altitude and low oxygen condition. The data showed 2 non-synonymous variations in coding region, while 5’UTR was completely conserved. The 3’UTR showed 2 more variations in Ladakhi samples. Further, the genotyping in 85 Ladakhi cattle for A1A2 alleles revealed that in Ladakhi cattle, A2 allele is predominantly present as reported for some of the other Indian breeds. The frequency of A2 allele was 0.90 and frequency of A2A2 genotype was found to be 0.79 in Ladakhi cattle. The present data strongly indicate that local cattle of Ladakh with higher frequency of A2 allele and A2A2 genotype is natural resource for A2 milk. Systematic efforts should be made for long term conservation and genetic improvement of this invaluable genetic resource of Ladakh.

Download Full-text

Bovine Milk: A1 and A2 Beta Casein Milk Proteins and their Impact on Human Health: A Review

Agricultural Reviews ◽

10.18805/ag.r-2126 ◽

2021 ◽

Author(s):

P. Chitra

Keyword(s):

Amino Acid ◽

Type I Diabetes ◽

Heart Diseases ◽

Age Groups ◽

Bovine Milk ◽

Milk Proteins ◽

Type I ◽

Beta Casein ◽

Casein Protein ◽

Proline Amino Acid

Milk is the ideal food for all age groups of human being. Milk consists of 87 per cent water and the remaining 13 per cent is the milk sugar lactose, protein, fat, vitamins and minerals. Casein is the chief component of the milk proteins of which about 30 per cent is beta-casein. The major beta-casein variants are A1 and A2. Beta-casein consist a chain of 229 amino acids. Cows that produce milk contain proline amino acid are called as A2 cows. A2 milk is found basically in indigenous cows and buffaloes of India. Around 5,000 years ago, a mutation occurred in this proline amino acid, converting it to histidine amino acid at 67 th position. Cows that have this mutated beta casein protein are called A1 cows. Different mutations bovine beta casein produce 13 genetic variants and out of these A1 and A2 are the most common. A1 β-casein is enzymatically broken down in the intestine to produce beta-casmorphin-7 (β-CM-7) which is an opioid peptide similar to morphine. BCM-7 interacts with the human gastrointestinal tract, internal organs and brainstem. BCM-7 adversely affects the immune response and is also considered as a risk factor for chronic heart diseases (CHD) and juvenile insulin dependent type I diabetes mellitus (DM-I). The original beta casein protein in bovine milk was A2. A2 is more comparable to the human beta casein than A1 in terms of digestive breakdown. Indigenous dairy breeds of cow (Red Sindhi, Sahiwal, Tharparkar, Gir and Rathi) and buffalo produce A2 milk and India is endowed with rich A2 dairy animals.

Download Full-text

Proteins of human milk. I. Identification of major components.

Clinical Chemistry ◽

10.1093/clinchem/28.4.1045 ◽

1982 ◽

Vol 28 (4) ◽

pp. 1045-1055 ◽

Cited By ~ 31

Author(s):

N G Anderson ◽

M T Powers ◽

S L Tollaksen

Keyword(s):

Human Milk ◽

Whey Proteins ◽

Bovine Milk ◽

Skim Milk ◽

Milk Proteins ◽

Relative Molecular Mass ◽

Isoelectric Points ◽

Beta Casein ◽

Dimensional Electrophoresis ◽

New Protein

Abstract Traditionally, human milk proteins are identified largely by reference to bovine milk. Hence, to identify the major proteins in human milk, we subjected human and bovine milk, in parallel, to high-resolution two-dimensional electrophoresis. Isoelectric precipitation at pH 4.6 was our criterion for distinguishing whey proteins from those of the casein complex. The alpha- and beta-caseins were identified on the basis of relative abundance, relative molecular mass, and relative isoelectric points. Kappa casein was identified as a series of four spots, which disappear from bovine skim milk treated with rennin (chymosin; EC 3.4.23.4) during the clotting process. Para kappa-casein does not appear on the standard ISO-DALT pattern after treatment of bovine milk with rennin, but does appear in BASO-DALT pattern, indicating its high isoelectric point. No protein disappeared from ISO-DALT patterns of human milk after rennin treatment, and no new protein comparable to bovine para kappa-casein appeared in the BASO-DALT patterns; this suggests that kappa-casein is absent from human milk. The proteins identified in human milk patterns include the alpha and beta casein families, lactalbumin, albumin, transferrin, IgA, and lactoferrin. Numerous additional proteins seen in patterns for human milk remain to be identified.

Download Full-text

A Comprehensive Evaluation of the Impact of Bovine Milk Containing Different Beta-Casein Profiles on Gut Health of Ageing Mice

Nutrients ◽

10.3390/nu12072147 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2147 ◽

Cited By ~ 1

Author(s):

Barbara Guantario ◽

Marzia Giribaldi ◽

Chiara Devirgiliis ◽

Alberto Finamore ◽

Elena Colombino ◽

...

Keyword(s):

Control Diet ◽

Protein Profile ◽

Bovine Milk ◽

Short Chain Fatty Acids ◽

Nutritional Deficiencies ◽

Gut Health ◽

Mice Model ◽

Positive Role ◽

Beta Casein ◽

The Impact

Ageing is often characterised by nutritional deficiencies and functional alterations of the digestive and immune system. The aim of the present study was to analyse the impact of consumption of conventional milk with A1/A2 beta-casein, compared to milk containing only the A2 beta-casein variant, characterised by a protein profile favouring gut health. Twenty-four ageing Balb-c mice (20 months old) were fed for 4 weeks, with either a control diet (CTRL), a diet supplemented with bovine milk containing A1/A2 beta-casein (A1A2) or a diet containing A2/A2 beta-casein (A2A2). Lymphocyte subpopulations, enzymatic activities, cytokine secretion, gut morphology and histopathological alterations were measured in different gut segments, while short-chain fatty acids (SCFAs) content and microbiota composition were evaluated in faecal samples. The A2A2 group showed higher content of faecal SCFAs (in particular, isobutyrate) of intestinal CD4+ and CD19+ lymphocytes in the intraepithelial compartment and improved villi tropism. The A1A2 group showed higher percentages of intestinal TCRγδ+ lymphocytes. Faecal microbiota identified Deferribacteriaceae and Desulfovibrionaceae as the most discriminant families for the A2A2 group, while Ruminococcaceae were associated to the A1A2 group. Taken together, these results suggest a positive role of milk, in particular when containing exclusively A2 beta-casein, on gut immunology and morphology of an ageing mice model.

Download Full-text

Expression analysis of the individual bovine β-,αs2- and κ-casein genes in transgenic mice

Biochemical Journal ◽

10.1042/bj3110929 ◽

1995 ◽

Vol 311 (3) ◽

pp. 929-937 ◽

Cited By ~ 35

Author(s):

M Rijnkels ◽

P M Kooiman ◽

P J A Krimpenfort ◽

H A de Boer ◽

F R Pieper

Keyword(s):

Mammary Gland ◽

Transgenic Mice ◽

Bovine Milk ◽

Regulatory Elements ◽

Regulation Of Expression ◽

Casein Gene ◽

Expression Levels ◽

Beta Casein ◽

Casein Genes ◽

High Level

To identify cis-acting regulatory elements involved in the regulation of expression of the casein genes, the bovine beta-, alpha s2- and kappa-casein genes were isolated from cosmid libraries and introduced into the murine germline. Bovine casein expression was analysed at the RNA and protein level. The bovine beta-casein gene, including 16 kb of 5′- and 8 kb of 3′-flanking region, appeared to be expressed in all 12 transgenic mouse lines analysed. In 50% of these lines expression levels in milk exceeded 1 mg/ml. Three lines displayed expression levels comparable with or well above (20 mg/ml) the beta-casein levels in bovine milk. Transgene expression was restricted to the mammary gland. Strong induction of expression occurred at parturition and thus resembled the bovine rather than the murine pattern. In spite of this high-level tissue-specific and developmentally regulated expression, beta-casein expression levels were integration-site-dependent, suggesting that not all elements involved in regulation of expression were included in this beta-casein clone. Neither the bovine alpha s2- nor the kappa-casein gene, including 8 kb and 5 kb of 5′- and 1.5 kb and 19 kb of 3′-flanking sequences respectively, were properly expressed in transgenic mice. However, they were transcribed in stably transfected mouse mammary epithelial cells. This indicates that regulatory elements required for high-level, mammary gland-specific expression are not present in the alpha s2- and kappa-casein clones used in this study and are probably located elsewhere in the casein gene locus.

Download Full-text

A1- and A2 beta-casein on health-related outcomes: a scoping review of animal studies

European Journal of Nutrition ◽

10.1007/s00394-021-02551-x ◽

2021 ◽

Author(s):

Daniela Kuellenberg de Gaudry ◽

Szimonetta Lohner ◽

Karin Bischoff ◽

Christine Schmucker ◽

Simone Hoerrlein ◽

...

Keyword(s):

Animal Models ◽

Scoping Review ◽

Animal Studies ◽

Bioactive Peptides ◽

Bovine Milk ◽

The Body ◽

Essential Information ◽

Population Type ◽

Health Related ◽

Beta Casein

Abstract Purpose Food-derived bioactive peptides may influence important physiological functions. An important example is beta-casomorphins, which are opioid peptides derived from A1 beta-casein in bovine milk and have been associated to be risk factors for non-communicable diseases in humans. A1 and A2 beta-casein are different with respect to the release of bioactive peptides, in particular BCM-7. However, evidence from human studies is limited and could be complemented with evidence derived from animal studies. We conducted a scoping review to identify animal studies investigating the effects of A1 beta-casein or BCM-7 compared to A2 beta-casein or any other intervention on health-related outcomes. Methods We systematically searched for relevant studies in two electronic databases (Medline, Embase; last search performed March 2020). Two reviewers independently undertook study selection and data extraction of included references. Results were summarized tabularly and narratively. Results We included 42 studies investigating various animal models, including rats, mice, rabbits, and dogs. Six studies investigated health-related outcomes of A1- vs. A2 milk, while most studies (n = 36) reported on physiological properties (e.g., analgesic effect) of BCM-7 as an opioid peptide. Included studies were extremely heterogeneous in terms of the study population, type of intervention and dose, and type of outcome measures. Conclusions Only a few studies comparing the effects of A1- and A2 milk were identified. More studies addressing this research question in animal models are needed to provide essential information to inform research gaps. Results from future studies could eventually complement research for humans, particularly when the body of evidence remains uncertain as is the case in the A1- and A2 milk debate.

Download Full-text