Study of amino acid transport in the intestine of higher animal, which had initiated into the concept of active transport and entertained the classical hypothesis of protein absorption in animal intestine, is still at a fairly primitive sgage of investigation. The present report reviews current status of knowledge and research results from the author's laboratory in this field, and aims to call readers' attention to the opportunity for definitive experiments with animal intestine. Nε-substituted L-lysine derivatives were found nontransportable and to inhibit competitively the transport of basic amino acids but entirely not of the neutral amino acid. The results were interpreted indicating the separateness of the substrate recognition and translocation processes involved in the transport mechanism. Evidence is reviewed for incompleteness of stereospecificity of transport mechanism. Those amino acids previously known to support growth and to maintain N balance in place of their L-isomers in animal nutrition were found among those amino acids which could induce positive transport potential and could be actively taken up by the intestine; the results are implicit that active transportability constitutes a prerequisite for effective utilization. Selected examples are discussed of changes in intestinal functions with different dietary conditions including semistarvation, feeding on diets containing one or two amino acids in excess of animal requirement, and daily rhythmic changes in meal-fed rats. Transport of both D- and L-isomers of various amino acids so far tested increased impartially after semistarvation. Kinetic analyses revealed that semistarvation induceda greater increase in maximum transport capacity but least effect on the affinity of the trans-port mechanisms. On the other hands excessive administration of certain amino acid lead to increase transport for the amino acid in concern; results can be regarded as an induction by the substrate amino acid. Daily rhythm of the transport mechanism was found synchronized to the time of feeding and to be possibly entrained by those rhythms occurring in the epithelial cells (protein synthesis). Some unanswered questions are reviewed regarding peptide transport in the intestine. And the emphasis is given to assess quantitative importance as well as to elucidate absorption mechanism(s) of peptide absorption, and to conduct experiments with peptide along the line of studies already carried out with amino acids.

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Multidisciplinary studies on Streptomyces subtilisin inhibitor (SSI) have been reviewed. SSI is a protein proteinase inhibitor isolated in a crystalline form from the culture broth of Streptomyces albogriseolus S-3253 by Murao et al. in 1972. This inhibitor exhibits very strong inhibition almost exclusively against alkaline serine proteases such as subtilopeptidases. SSI is composed of two identical subunits of MW 11, 500 (113 amino acid residues), and acts in a dimeric form under the ordinary conditions to inhibit two moles of enzyme per mole of dimer (MW 23, 000).
Stability, easy crystallization, molecular size, unique specificity of inhibition, relative easiness in obtaining large amount of preparation due to microbial production, and the fact that three dimensional structure of subtilisin BPN', which is most strongly inhibited by this inhibitor, has been elucidated, all make SSI one of the most suitable subjects for the study of the specific interaction between proteins. Co-operative studies centered onthis inhibitor started in 1973 among several laboratories in Japan. The primary structure of SSI has been elucidated in 1974, and a preliminary report on its three dimensional structure based on 2.3Å-resolution X-ray difraction pattern has appeared in 1977.
Research topics reviewed here include: molecular weight determination; amino acid composition and the primary structure; X-ray crystallography; states of mino acid residues (solvent perturbation, spectrophotometric titration); hydrogen-deuterium exchange; optical properties (UV, fluorescence); denaturation (heat, acid); dissociation into monomer; inhibition spectrum; equivalence of inhibition and binding; isolation of the enzyme inhibitor complex; reactive site against the enzyme; affinity to enzymes (inhibitor constants); changes in the states of amino acid residues on the interaction of the enzyme inhibitor complex; reactive site against the enzyme; affinity to enzymes MCD); kinetics of association of the inhibitor and the enzyme; effects of chemical modification of amino acid residues (of SSI, of the enzyme); utilization of SSI (affinity chromatography on immobilized SSI).

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Several models for pattern formation by cell differentiation were critically described. They were classified into the two main types. The first type of models is based on the concept of positional information formulated by Wolpert from the generally observed fact that cells differentiate according to their relative positions in a developing system. The two models were illustrated as those which materialize the concept: a diffusion model of Laurence, Crick and Munro for pattern formation in insect epidermis and the phase-shift model devised by Goodwin and Cohen. In contrast, the second type of models is based on the idea that pattern formation can be explained by considering interactions among cells in a developing system without resorting to a mechanism specifying positions of individual cells. Two examples of this sort were presented: a model of Gierer and Meinhardt for pattern formation in hydra and a diffusion-reaction model of Turing. An attempt was made to formulate the process of specification of cell state which leads to differentiation of a cell. Finally, the significance and te interpretation of a model were discussed.

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