Harold F. Deutsch

Chemistry and Biology of α-Fetoprotein

Alpha-Fetoprotein (AFP) is a product of specific fetal tissues and of neoplastic cells of hepatocyte or germ cell origin in adults. This protein belongs to a gene family that is phylogenetically most closely related to serum albumin. Its primary, secondary, and tertiary structural aspects appear similar to the three-domain concept proposed for the latter protein. The primary sequence of AFP departs most widely from serum albumin in the first 135 amino acid residues, with about 42% of the remaining 590 residues of the human proteins being identical. Some evidence exists that there are limited sequence differences in the AFP of a given animal species. AFP shows considerable charge heterogeneity that appears to relate mostly to its glycoid moiety. The proteins of some species such as the rat show more pronounced heterogeneities than that of humans. The variations in extent and type of glycosylations are evidenced by differences in the binding to various lectins. These interactions are being extensively explored in attempts to differentiate the sources of the protein produced by various normal and neoplastic cells and may provide valuable diagnostic methods. AFP, like serum albumin, shows relatively strong binding affinities for a variety of ligands. The most notable difference is the strong preferential binding of polyunsaturated fatty acids by AFP. This protein may play a role in transporting these substances to developing and to malignant cells. Various agents affect the synthesis of this protein both by specific fetal tissues and by neoplastic cells. Marked differences in the responses of cells, particularly those of neoplastic types, are indicative of variations in the genetic factors responsible for control of its synthesis. The subject of the genomic repression of the synthesis of AFP seen in fetal life upon maturation of the liver and the reoccurrence of synthesis upon malignant conversion of hepatocytes and of certain germ cells are of particular interest. The regulation of the closely related AFP and albumin genes is providing a powerful and attractive model to examine molecular events in the activation and inactivation of specific genes during development and in oncogenic processes. Extensive measurements of AFP during pregnancy and in the course of neoplasias, notably hepatoma, are being made to aid in following changes in such developments. Various specific physiological roles for this protein are also being proposed. One of these is its possible action in the regulation of immune processes.(ABSTRACT TRUNCATED AT 400 WORDS)

The levels of superoxide dismutase and catalase in human tissues as determined immunochemically

Abstract The levels of Superoxide dismutase and of catalase have been determined immunochemically by the single radial diffusion technique in a variety of human tissues. The results indicate that brain, liver, erythrocytes, kidney, thyroid, pituitary, and adrenals are rich sources of Superoxide dismutase. Some tissues rich in Superoxide dismutase such as cerebral cortex, thyroid, and pituitary have very low levels or lack catalase.

Some physical-chemical properties of chicken γ-globulins and their pepsin and papain digestion products

Abstract Chicken γ-globulin has been purified and subjected to physical-chemical and to enzymatic degradation studies. The normal γ-globulins have a molecular weight near 206,000, have an isoelectric point near 5·2, and contain near 3·1 per cent hexose. Electrophoretic “fast” and “slow” components are produced with both papain and pepsin. The papain fast components retain some antigen combining activity. It is suggested that the normal chicken γ-globulins are more similar to the γA- than to the γG-globulins of mammalian species.

Hinge-regIon deletion localized in the IgG1-globulin Mcg☆

Abstract The H chain of the IgG protein Mcg has a deletion of 15 amino acids which starts at a position 216 residues from the amino terminal end of the molecule. This protein is thus complementary to those seen in H chain disease where the deletion occurs within the first 215 amino acid residues and a normal structure is resumed at position 216.

The preparation of crystalline ceruloplasmin from human plasma

Abstract Crystalline ceruloplasmin may be readily prepared in good yield from human serum or plasma by procedures based on chromatography on diethylaminoethyl-cellulose. As prepared, this protein appears to be made up of a series of molecules of varying solubilities. Repeated crystallization followed by a Chromatographic separation step at neutral pH provides a ceruloplasmin containing 8 atoms of copper per 150,000 g. protein and one that shows a single component on electrophoretic and ultracentrifugal assay.

Studies on papain produced subunits of human γG-globulins—II: Structures of peptides related to the genetic Gm activity of γG-globulin Fc-fragments

Abstract Two tryptic pentapeptides of papain digest Fc-fragments of myeloma γG-globulins which appear to be related to the Gm-genetic activity of the parent molecules have been isolated and their primary structures determined. The one associated with Gm-a activity is Asp-Glu-Leu-Thr-Lys. It appear that the Fc-fragments not possessing Gm-a activity contain a Met-Glu-Glu-Thr-Lys sequence. Both of these peptides are derivatives of an undecapeptide whose hexapeptide amino terminal portion is identical and which has the structure Thr-Leu-Pro-Pro-Ser-Arg.

Rapid method for preparation of crystalline human ceruloplasmin from Cohn Fraction IV-1☆

Abstract Crystalline ceruloplasmin has been prepared in high yield by a relatively rapid method from Cohn Fraction IV-1 of human plasma. The material contains near eight molecules of copper per 160,000 g. protein. It shows a single component on electrophoretic and ultracentrifugal assay.

Isolation of equine muscle carbonic anhydrase in crystalline form

Abstract A relatively simple procedure for the isolation of equine muscle carbonic anhydrase (CA-III) in crystalline form has been developed. An important aspect of the method, which should find ready application to this enzyme from other species, is the alkylation of the readily reactive cysteine residues prior to starting the fractionation.

A new λ-chain gene☆

Abstract A total of six human λ-chain proteins have been found which possess three hitherto unreported constant region amino acid substitutions. The three variant residues are always found in association with the previously described Oz (−) and Kern (+) substitutions. λ-Chains containing the three variant replacements have also been demonstrated in the light chain fractions of IgG derived from pooled normal human serum and from the sera of each of four individuals. In addition, studies of monoclonal λ-chains have demonstrated that the variant constant region sequence is found in association with a specific variable region substitution. The results indicate that this isotypic λ-chain constant region is the product of a specific gene.

Human carbonic anhydrases. VII. A new C type isozyme in erythrocytes of American Negroes

An unusual erythrocyte carbonic anhydrase C type isozyme tentatively designated as H has been found in American Negroes. It has an electrophoretic mobility near that of carbonic anhydrase B. In about 18% of the individuals studied the H isozyme replaces half of the normal C isozyme, and in about 1% of this population only the H isozyme is present.