19521 NUTRITION REVIEWS 113

deiice of enlarged hocks may vary from 40 per cent to 70 per cent. Wit,h such variations

PYRIDOXAL PHOSPHATE

It is iiow established that cystirie is not syiithesized i n the body from catabolic nitrogenous sources, but rather that i t re- c.ei\es its sulfur from methioriiiie by way of liomocysteine, and the remainder of the carbon structure from serine. The intermedi- ate in this transformation has been isolated (F. Riiikley, J . Bid. C‘hcm. 191, 531 (1951)). The enzyme prcparat ion employed was made from rat livers; they were homogenized in 0.2 molar potassium chloride and 0.01 molar sodium citrate, ventrifuged and the residue discarded. By fractionation with cold ethyl alcohol two enzyme systems were ohtailled, one apparently capable of effect- ing :L synthesis of the intermediate from liornocysteine and serine, and the other producing cysteine as one of the reaction products. Having prepared the synthesizing enzyme, it was possible to assay the cleavage enzyme, and vice versa. The intermediate produced by the rcactioii of the syrithesizirig enzyme upon a mixture of DL-homocysteine zliicl m-serine was isolated from the digest aud shown t o be L-cystathionine.

Further studies (F. Binkley, G. M. Christensen, and W. N. .Jeusen, J . Riol. (‘hcm. 194, 109 (1952)) on the properties of the enzyme mixtures have shown that solutions of the enzymeb can be inactivated by aging in a refrigerator or by dialysis :gainst distilled water. It thus was possible to study the coenzymes involved in the over- all synthesis of cysteine, as well as in the separate synthesizing and decomposing phases of the reaction. Pyridoxal phosphate

between experiments the .r-alidit,y of some of the conclusions must l x questioiied.

AND CYSTINE SYNTHESIS

added to the aged eiizyme solut ioiis iiicwased both the synthetic and tlie c.le:iv:ige activity as measured by the concciit rat ioiis of cystathioiiint a i d cysteiiie resptvtiyely, Even freshly prepared enzyme preparut ions show some activation by py r idod phos- phate. When djeiikolic acid, 1,-cystathioniue or L-allocystathiouine were used as sub- strates, the stimulating artion of pyridoxal phosphate 011 the cleavage enzyme IVUS

observed. In order to demoiist rate the cwiizyme

action of pyridosiiie in another nay, ctizynie preparations were made from livers of rats subjected to various dietary adjustments: one group of rats u as given 4-aminopteroyl- glutamic acid, another group was deprived of folic acid, and still another group was given a pyridoxine-deficient diet. In com- parison to the results obtained with the liver enzymes of the control rats, only the livers of the pyridoxine-deficient group yielded preparations of low potency with respect to synthesizing and cleavage ell-

zymes. Furthermore, the addition of pyridoxal phosphate to both synthesizing and cleavage enzymes produced a striking response in activity, of greater magnitude than observed when the vitamin was added to preparations from the coiitrol animalh. The foregoing is conviiiciiig espci.iment:d evidence that pyridosal phosphate i:, the co-factor in the enzyme systems iiivol\xd i n the transfer of sulfur in tlie course of the biosyiithesis of cysteine.

PERNICIOUS ANEMIA IN CHILDHOOD

Although pernicious anemia is usually a dizease of adult life with :I peak iiicideticc occ.ur.riiig in the siitli c l c c d c , it may occur

during childhood. The essential defect in pernicious anemia is nt)senc*e of the iutrinsic factor of Castle from the gastric secretions,

114 NUTRITION REVIEWS [April

with failure to absorb the extrinsic factor present in foods, now considered to be identical wit>h vitamin BI2. This defect is associated with histamine-refractory achlorhydria, macrocytic anemia, arrest of maturation of the bone marrow at the megaloblastic level, a response to specific treatment, and the necessity of continued therapy to prevent relapses. Other common findings are combined system disease of the brain and spinal cord, gastroint.est,inaI lesions, and premature graying of the hair. The number of cases of pernicious anemia fulfilling t,hese criteria and occurring in children is extremely small, only 7 cases being recognized by E. H. Reisner, ,J. A. Wolfe, R. J. McKay, and E. F. Doyle (Pediatrics 8, 88 (1951)). B. Benjamin (Am. J. Dis. Child. 76, 143 (1948)) reported a case in which absence of the intrinsic factor was suggested by the R.eimann t,echnic (the failure of the gastric juice tjo potentiate the effect of oral liver in a patient with proven periiicious anemia in relapse), de- spit,e the iiiconstant presence of free hydro- chloric acid in the gastric secretions. This observat’ion suggested to Reisner et al. that persistent achlorhydria might not be a necessary diagnostic feature of pernicious anemia in childhood.

Four cases, t,wo pairs of siblings, in which such a diagnosis was established have been reported by these workers. In 3 of these, free hydrochloric acid was found, although achlorhydria developed in one of them after seven years of observation. The diagnosis was confirmed by t>he absence of any other known cause for anemia and t,he demonstra- tion that small oral doses of vitamiu Biz

were ineffective without the addition of normal gastric juice. A IZeimanii test was negative in one of these patients.

Twelve other cases which were felt to represent true pernicious anemia in child- hood were found in the literature when the possibility of a defective intrinsic factor production in the presence of free hydro- chloric acid ~ v a s considered. Certain inter- e h n g observat,ioiis were made on this group of 16 cases. Consaiiguinity or il familial history of the disease was found in 8 of the 14 families represented. The onset could frequently be traced back to infancy. Free hydrochloric acid was present in the stomach in 8 of these cases. There was evidence of combined system disease iii 5, with very severe involvement which responded to specific therapy in a child of 3 years. Glossitis, gastrointestinal lehions, and even graying of the hair have been reported.

These studies have suggested that per- nicious anemia may occur in children more frequently than has been supposed and that histamine-refractory achlorhydria may iiot be essential to the diagnosis if evidence for the absence of intrinsic factor is obtained. Benjamin (Zoc. cit.) has suggested that the defect in the stomach may hare been a coii- genital one in his case, the anemia developing when transplacental stores of the matura- tion factor were exhausted. The absence of spontaneous remissions in several children in this group would also suggest that the defect might be complete from birth rather than developed later as a “degenerative” process. Pernicious anemia should be con- sidered in the differential diagnosis of all relapsing anemias of childhood.

COMPLEX COMPOUNDS OF FLUORINE IN CARIES CONTROL

The discovery that fluoride is the etiologic fluoride to the communal water supply as a factor in the development of dental fluorosis public health measure, thus taking ad- was followed by the repeated demoiistration vantage of the anticariogenic action of that this ion likewise exerts a protective fluoride. Inasmuch as the entire water sup- action against dental caries. As a result, ply of a given communit>y is ordinarily many communities are adding sodium fluorinated the item of cost is significant; in