Phosphate in the Diet

The relationship between calcium and phosphate metabolism is very complex. The quesbon of the ratio of calcium/phosphate in the diet may be raised when discussing diets needed to support maximal growth or when discussing pathological phenomena, such as hypocalcemia, osteoporosis, kidney stone formation, and the ealcificabtin of soft tissues. A firm grounding in one or two relationships in calcium... 

No studies were located regarding cardiovascular effects after acute- or chronic-duration oral exposure in animals. In male weanling Wistar rats (5-6 per group) given strontium as strontium phosphate in the diet for 4-6 weeks, hemorrhage (unspecified) occurred at 2,820 mg strontium/kg/day, possibly related to the increased mortality at this dose level, but not at or below 1,270 mg Strontium/kg/day (Kshirsagar 1976). 

As mentioned before, only a small amount of riboflavin is present in foods as the free form or as riboflavin phosphate. In the diet, riboflavin occurs... 

Since phosphate is also involved in calcium homeostasis via its effects on the renal 25-OHD-la-hydroxylase (and not involving PTH), an imbalance of calcium and phosphate in the diet, or impairment of absorption, can lead to derangement of the control mechanism. It is of interest in relation to food safety evaluation that, in rats, calcium deposition in the kidney (nephrocalcinosis) has been observed in a number of studies on modified starches and microbial biomass . In the latter case, rats fed Candida utilis biomass rich in phosphorus and low in calcium developed nephrocalcinosis, but when the Ca/P ratio was adjusted to unity, renal changes were minimal. There is a clear lesson to be learned here if dietary imbalance per se can cause, or increase the severity of, pathological lesions, particular caution has to be exercised in the design and interpretation of toxicity tests where the test material is included in the diet at high concentrations. 

Genetic deficiency of fructokinase is benign and often detected incidentally when the urine is checked for glucose with a dipstick. Fructose 1-phosphate aldolase deficiency is a severe disease because of accumulation of fructose 1-phosphate in the liver and renal proximal tubules. Table 1-12-4 compares the two conditions. Symptoms are reversed after removing fructose and sucrose from the diet. 

The development and maintenance of healthy bone depends in part on an adequate supply of dietary calcium. Although phosphate is absolutely required for the mineralization of bone, it is abundant in the diet. If one gets enongh to eat, one gets enough phosphate. The same is not necessarily trne for calcinm and many people snpplement their diet with a preparation of calcium, frequently calcinm glnconate or calcium citrate. More follows below about the chemistry of bone when we get to a consideration of calcium. 

Figure 5.1 The structure of a glycerophospholipid. A simple diagram showing the charges on the head group. In this struction, palmitic and oleic acids, provide the hydrophobic component of the phospholipids and choline (and four bases) and the phosphate group provide the hydrophilic head. The unsaturated fatty acid, oleic acid, provides a kink in the structure and therefore some flexibility in the membrane structure which allows for fluidity. The more unsaturated the fatty acid, the larger is the kink and hence more fluidity in the membrane. Cholesterol molecules can fill the gaps left by the kink and hence reduce flexibility. Hydroxyl groups on the bases marked are those that form phosphoester links. Choline and inositol may sometimes be deficient in the diet so that they are, possibly, essential micronutrients (Chapter 15).

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

The first step in glycolysis is the phosphorylation of glucose to give the ester glucose 6-phosphate. The glucose starting material may well have come from hydrolysis of starch obtained in the diet, or by utilization of glycogen reserves. 

Nicotinate and nicotinamide, together referred to as niacin, are required for biosynthesis of the coenzymes nicotinamide adenine dinucleotide (NAD"") and nicotinamide adenine dinucleotide phosphate (NADP" ). These both serve in energy and nutrient metabolism as carriers of hydride ions (see pp. 32, 104). The animal organism is able to convert tryptophan into nicotinate, but only with a poor yield. Vitamin deficiency therefore only occurs when nicotinate, nicotinamide, and tryptophan are all simultaneously are lacking in the diet. It manifests in the form of skin damage (pellagra), digestive disturbances, and depression. 

In chronic 2-year feeding studies of the mixed isomer, there was no evidence of carcinogenicity in rats given up to 300 ppm or mice given up to 250ppm in the diet." Tricresyl phosphate was not mutagenic in Salmonella lyphimurium, nor did it induce chromosomal aberrations or sister chromatid exchange in Chinese hamster ovary cells."... 

Cholecalciferol (D3) and its active form 1,25-di-hydroxycholecalciferol are only to a certain extend vitamins because they can be synthesized by the human body. However deficiencies resulting in rickets in children and osteomalacia in adults do exist. Cholecalciferol can be synthesized by humans in the skin upon exposure to ultraviolet-B (UVB) radiation from sunlight, or it can be obtained from the diet. Plants synthesize ergosterol, which is converted to vitamin D2 (ergocalciferol) by ultraviolet light. Vitamin D2 may be less active in humans. Vitamin D promotes uptake of calcium and phosphate in the intestine and it stimulates osteoclasts to break down hydroxyapatite and release calcium into blood. Vitamin D is discussed in more detail in Chapter 24, Section V.a. 

Several microbial species (in particular fungi) produce phytases (EC 3.1.3.8). The incorporation of suitable, microbially derived phytases in the diet can confer the ability to digest phytic acid on the recipient animals. This would have a threefold beneficial effect the anti-nutritional properties of phytic acid would be destroyed a lesser requirement for feed supplementation with inorganic phosphorous wottld exist and reduced phosphate levels would be present in the faeces. Several trials have confirmed that the inclusion of phytase in animal feed promotes at least some of these effects. However, the enzyme is not yet used in many cormtries. This may be explained, in part, by the fact that most microbial species only produce low levels of phytase activity which, obviously, has an effect on the cost of the finished product. It seems likely that widespread utilization of phytase within the industry will only be made possible by the production of this enzyme from recombinant sottrces, and at least two major enzyme companies are marketing such an enzyme for a nttmber of years now. 

Dietary inoiganic phosphates have been shown to piotect expeiimental animals against dental caries. Orthophosphates were effective cariostats, but NjuP Oj and NasPgOio were not. Dicalcium phosphate, CaHPCL. did not decrease dental caries unless a high level of NaCI was also included in the diet. 

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