Search PubMed⌕ Search

Biomedical subjects

H Krebs

Publications and source records attributed to H Krebs.

At least 37 records · Page 2Linked to original sources
PubMed1985

Native-like folding intermediates of homologous ribonucleases.

The mechanism of the slow refolding reactions of four different pancreatic ribonucleases from ox, sheep, red deer, and roe deer has been investigated. Refolding kinetics of these proteins were very similar. In particular, a native-like intermediate, IN, was shown to be populated on the slow refolding pathway of all ribonucleases. We conclude that, similar to the stability of the folded proteins, the pathway of slow refolding has been conserved despite the differences in amino acid sequence and the varying number of proline residues.

Animals↗
PubMed1985

Decreased serotonin content of embryonic raphe neurons following maternal administration of p-chlorophenylalanine: a quantitative immunocytochemical study.

Previous studies from this laboratory have suggested that serotonergic (5-HT) neurons may influence the differentiation of their embryonic target cells in the developing rat brain. The present study was designed to determine whether or not maternal p-chlorophenylalanine (pCPA) administration could deplete serotonin (5-HT) in developing 5-HT neurons during embryonic days 13-15, when the effects of pCPA on neuronal genesis have been observed previously. For this study, pCPA was administered to timed-pregnant rats and embryos were sacrificed at two different gestational ages, embryonic days 13-14 (E13-14) and 14-15 (E14-15). Immunotitration experiments were carried out on tissue sections, using an antiserum to 5-HT-hemocyanin conjugates to obtain a relative estimate of the amount of 5-HT contained within individual 5-HT neurons of embryos from pCPA-treated and control mothers. Diminished immunoreactivity as a consequence of addition of increasing amounts of antigen was then quantitated on a relative scale by comparison with the amount of immunoreactivity present when no antigen was added to the primary antiserum. Two major findings resulted from this study: maternal pCPA treatment depleted 5-HT by approximately 50% in developing 5-HT neurons at embryonic ages E13-14 and E14-15, but depletion appeared to be greatest in the youngest embryos; developing 5-HT neurons increased their content of neurotransmitter by approximately 10-fold during this one day of embryonic development, an effect which could be observed in both pCPA-treated and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Folding of homologous proteins. The refolding of different ribonucleases is independent of sequence variations, proline content and glycosylation.

The refolding kinetics of four different pancreatic ribonucleases have been compared. Bovine and ovine RNAase contain 4 proline residues, red deer RNAase has 5 prolines, the enzyme from roe deer 6 prolines. Despite the variation in the amount of prolines, all four proteins show a constant value of 20% fast refolding species UF. The extra proline residues of the deer enzymes do not increase the amount of slow refolding species US. Consequently these residues may be non-essential for folding. Despite many differences in the amino acid sequence, the rates if the fast and slow refolding reactions are very similar for all investigated ribonucleases. This indicates that the pathway of refolding has been conserved during evolution, i.e. the positions where amino acid substitutions occur are not critically important for the rate-determining steps of the folding process. A carbohydrate chain attached to ribonuclease does not alter the folding properties of the protein: RNAase A and RNAase B from roe deer show identical refolding kinetics.

Amino Acid Sequence↗
PubMed1981

The evolution of metabolic cycles.

The function of the citric acid cycle is to convert efficiently the energy released during the combustion of acetate into the energy stored in the pyrophosphate bonds of ATP. The cycle is almost twice as efficient as feasible alternatives of acetate combustion, such as a direct pathway via glycollate, glyoxylate, formaldehyde and formate. The reason is that the first stage of acetate degradation cannot be a dehydrogenation; it must be an oxygenation by molecular oxygen. Thus the cycle must have evolved because in a competitive environment the chances of survival are greatest if resources are optimal. Analogous considerations apply to the evolution of other metabolic cycles.

Adenosine Triphosphate↗
PubMed1981

[Integration of the mentally handicapped (author's transl)].

The integration of handicapped persons into the family and society has almost become a slogan. The expression is often used very uncritically, but the necessity for such efforts remains undisputed. Examples are given to show what approaches are possible and also what forms of integrational endeavors are unreasonable for the mentally handicapped and which are in no way always to be considered as suitable for the handicapped person. Under this catchword the full time establishments (institutions, psychiatric clinics with oligophrenic departments and homes) for the mentally handicapped are also considered, but equally critically. A discussion on the widely used nomenclature in the language of psychiatry, in textbooks or dictionaries which are not all encouraging for integration or even particularly human, is informative.

Education of Persons with Intellectual Disabilitie↗
PubMed1981

Roles for serotonin in neuroembryogenesis.

Possible non-transmitter roles for 5-HT in different phases of early neuroembryogenesis have been discussed based upon experimental evidence from the rat and chick. Fluorescence histochemical studies have demonstrated sites of uptake and synthesis of 5-HT in the chick embryo during the first few days of incubation. These sites are located in discrete regions of the notochord and floor plate of the neural tube as well as in extra-neural regions such as the somites and primitive gut. The 5-HT patterns are distinctly different from those observed for the uptake and synthesis of norepinephrine in embryos of the same age. Spatio-temporal changes in the distribution of these sites during closure of the neural tube suggest a role for 5-HT in various aspects of neural tube development. Moreover, the non-overlapping localization of 5-HT and norepinephrine raises the possibility that these two amines may exert different and perhaps cooperative influences on early neurogenic processes in the chick. In the rat, autoradiographic and biochemical studies concerning the consequences of 5-HT depletion in the embryo for development of different brain regions have provided evidence that 5-HT acts as a "differentiation signal" regulating the time of neuronal genesis in those cell populations which will eventually receive 5-HT innervation. Although the details of this system are as yet unknown, these studies suggest that 5-HT (and possibly the other monoamine transmitters) may actually "mold" the construction of their own circuitry during neurogenesis. Further, the ability of drugs and stress to interact with this process during that period of gestation when the monoamines are required as humoral signals suggests that maternal influences can interfere with ontogeny of this circuitry during pre- and possibly postnatal development. It is not yet clear whether the data in chicks and rats can be directly analogized from the one species to the other. Nevertheless, the evidence that sites of 5-HT uptake and/or synthesis are present during the earliest phases of neurogenesis in the chick and the observation that 5-HT depletion can alter the time of genesis of 5-HT target cells in the rat provide a new context for the consideration of possible actions of 5-HT prior to its role as a neurotransmitter substance.

Animals↗
PubMed1981

Maternal influences on tryptophan hydroxylase activity in embryonic rat brain.

Maternal treatment with p-chlorophenylalanine strongly inhibits brain tryptophan hydroxylase (TPH) activity in the embryo, whereas administration of tryptophan significantly elevates the activity of this enzyme. Maternal stress, glucocorticoid injections, or a corn diet (low in tryptophan) do not change embryonic TPH activity, however. Since TPH is thought to be rate-limiting for serotonin (5-HT) synthesis in the developing animal as well as in the adult altered TPH activity as a result of maternal influences could change 5-HT synthesis in the embryo. If 5-HT is a developmental signal in the early differentiation of specific neurons during embryogenesis, as previously suggested, such maternal influences could affect this process, resulting in altered neuronal genesis in those brain regions receiving a serotonergic innervation.

Animals↗
PubMed1981

Deprenyl in Parkinson disease.

(-)Deprenyl, a specific monoamine oxidase subtype B inhibitor (MAOI-B), has been reported to be a safe and valuable adjunct to conventional treatment of parkinsonism. A double-blind, clinical comparison of (-)deprenyl with placebo was undertaken in 11 parkinsonian patients; the efficacy of 10 mg daily was studied over 4 weeks. In four cases the clinical score for parkinsonian deficits improved during deprenyl therapy, and in five it deteriorated; there was no change in one patient. Two subjects failed to complete the study. (-)Deprenyl induced euphoria and insomnia. It was concluded that any advantages deriving from the use of (-)deprenyl in parkinsonism are limited, and probably dominated by its elevation of mood. Biochemical analysis failed to reveal any significant increase in platelet or plasma catecholamine concentrations during deprenyl therapy. There was, however, a significant decrease in plasma epinephrine (p < 0.05) and platelet MAO activity (p < 0.005).

Adult↗
PubMed1980

[Present problems of the mentally handicapped (author's transl)].

At the present time mental handicap has become a multidimensional polydisciplinary task. A structurally static consideration of the pathological anatomic data as an unalterable situation due to cerebral organic deficiency or classifying the handicap as a disease is no longer tenable. Therefore training programs with a joint medical and medical pedagogic approach are becoming increasingly important. Yet there still remains much to clarify in causal - and therapeutic - research. The situation of the parents and sublings in the family with a handicapped child is consequently subject to special problems and psychosocial stress.

Child↗
PubMed1980

Rate enhancement of reconstitution of glyceraldehyde-3-phosphate dehydrogenase by a covalently bound coenzyme analog.

Kinetic analysis of the in vitro reconstitution of glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] from yeast showed that both oxidized and reduced coenzyme enhance the transconformation reaction, which is rate limiting in the sequential folding-association process at high enzyme concentrations (Krebs, H., Rudolph, R. & Jaenicke, R. (1979) Eur. J. Biochem. 100, 359-364). In the present study the reconstitution of the enzyme has been analyzed after covalent modification with the coenzyme analog 3-[(3-bromoacetylpyridinio)-propyl]adenosine pyrophosphate. Reconstitution of the modified enzyme, as determined by the regain of the native tryptophan fluorescence, is found to be more then 10 times faster than refolding of the unmodified apoenzyme and more than 5 times faster than that of the unmodified holoenzyme. Various degrees of denaturation and the presence of up to 0.4 M guanidine . HCl do not affect the rate of reconstitution of the modified enzyme. The kinetic effect of free or covalently bound coenzyme is discussed in terms of a decrease in free energy of the native or native-like structure or in terms of a decreased activation energy of rate-limiting steps in the process of reconstitution. Stabilization of the dimeric intermediate or acceleration of its transformation seems to be the most likely explanation for the observed effect of free or covalently bound coenzyme on the rate of reconstitution.

Adenosine Diphosphate↗
PubMed1980

Multiple sclerosis in twins.

We studied 30 sets of twins in whom one or both was suspected of having multiple sclerosis (MS). In 24 pairs, a firm clinical diagnosis was made on each twin. Among these 24 pairs, 6 of 12 monozygotic twins were concordant for clinical MS, compared with 2 of 12 dizygotic twins. Of those over the age of 50, two of three monozygotic pairs were concordant, but neither of the two dizygotic twin pairs were concordant. Because ascertainment was primarily through public announcement, this series may be biased in favor of twins concordant for MS. The individuals within monozygotic concordant twin pairs exhibited wide differences in severity and age at onset of disease; the more recently affected twin tended to have a lower cerebrospinal fluid (CSF) IgG and a higher IgM level. Although the frequency of HLA-B7 and Dw2 in this twin population was high, the HLA makeup did not differ appreciably between concordant and discordant MS twins. Furthermore, the two DZ-concordant twins were HLA-nonidentical. Unexplained neurologic signs were found in three asymptomatic twins, and a high proportion of clinically normal twins had abnormalities of CSF immunoglobulins. These latter findings suggest a high incidence of subclinical MS in this population.

Adult↗
PubMed1979

Influence of coenzyme on the refolding and reassociation in vitro of glyceraldehyde-3-phosphate dehydrogenase from yeast.

Kinetic analysis of the reactivation in vitro of glyceraldehyde-3-phosphate dehydrogenase from yeast in the presence of NAD+ suggested that transconformation reactions of inactive monomers and their subsequent association to native tetramers are responsible for the sigmoidal relaxations [R. Rudolph et al. (1977) Eur. J. Biochem. 81, 563-570]. Comparison with the reactivation behaviour in the absence of coenzyme was not feasible at this stage due to the instability of the apoenzyme. In the present study, solvent conditions were established which allowed both apoenzyme and holoenzyme to exhibit high stability. The apoenzyme is stable in phosphate buffer; but if excess NAD+ and phosphate are present (both of which stabilize the enzyme if applied separately), destabilization occurs. Protection of functional groups against oxidation by addition of a reducing agent and by degassing and preventing contact with air, increase the stability. Only partial stabilization can be achieved in the presence of NADH. Comparing the kinetics of reactivation in the presence and absence of coenzymes shows that both oxidized and reduced coenzyme enhance the rate of reactivation significantly, and to the same extent. The kinetic effect of coenzyme binding to the refolding polypeptide chain is discussed in terms of the stabilization of intermediates or end products of reconstitution on the one hand, and acceleration of folding and association reactions, on the other.

Drug Stability↗