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Biomedical subjects

N Marks

Publications and source records attributed to N Marks.

At least 55 records · Page 3Linked to original sources
PubMed1981

Protracted form of Canavan's disease: case history and protein kinase activity of membrane fractions.

Clinical and morphological findings in an 8-year-old Jewish girl with spongy leukodystrophy are presented. Ultrastructural changes indicated that this may be a form of Canavan's disease with some atypical features. Biochemical measurements indicated that synaptosomal membranes prepared from the striatum but not from the cerebral cortex were deficient in protein kinase activity based on incorporation of 32P into proteins. Both areas contained the same spectrum of proteins. Cyclic AMP (cAMP) measurements indicated no significant differences between brain areas, or when compared to tissue obtained from a stillborn and a 5-year-old child.

Brain↗
PubMed1981

Conversion of Met-enkephalin-Arg6-Phe7 by a purified brain carboxypeptidase (cathepsin A).

A carboxypeptidase A-like enzyme known as cathepsin A was purified from rat brain by extraction with Triton X-100, followed by chromatography on DEAE-Sephadex A-50 and gel-filtration. Purified enzyme was devoid of contamination of tryptic-like enzymes, by dipeptidyl carboxypeptidase (angiotensin converting enzyme) and of enkephalinnases cleaving the Tyr-Gly and Gly-Phe bonds of Met-enkephalin. Incubation of purified enzyme with Met-enkephalin-Arg6-Phe7, a naturally occurring enkephalin surrogate, was accompanied by the release of three products as detected by reverse phase HPLC. Subsequent amino acid analysis identified these as Phe, Met-enkephalin-Arg6, and Met-enkephalin, indicating cleavage at the Arg6-Phe7 and Met5-Phe6 bonds. Breakdown followed a precursor-product-relationship with the hexapeptide appearing as an intermediate and the pentapeptide as the final product. The Km for cleavage of the Arg-Phe site was 0.09 mM. Rates of cleavage of hexa- and heptapeptide accord with those found for synthetic N-protected dipeptide substrates. Cathepsin A does not act as an enkephalinase in the accepted sense, since no breakdown of Met-enkephalin was observed.

Amino Acid Sequence↗
PubMed1981

Peptide processing in the central nervous system.

1. A thiol proteinase from human pituitaries was purified approximately 400 fold and shown to have different chromatographic properties from that of calf brain. Among substrates cleaved were myelin basic protein, histones, beta-lipotropin, neurophysin, and Substance P. 2. The enzyme showed properties associated with a cathepsin-B like enzyme: dependence on -SH groups, pH optimum of 6.5, inhibition by leupeptin and a synthetic analog, Boc-D-Phe-Pro-arginal, and cleavage of dipeptidyl arylamides with basic residues adjacent to or penultimate to the chromatographic grouping. 3. Membranes present in the P2 fraction of rat brain contained three or more enkephalinases when submitted to DEAE-cellulose chromatography. Further purification on an IgG-Sepharose affinity column prepared with antibody to lung angiotensin converting enzyme indicated the presence of dipeptidyl carboxypeptidase(s) with properties distinct from those of ACE. In addition, the DEAE-cellulose fractions contained various aminopeptidase activities when tested with Leu-Gly-Gly, Leu-Nap, and Ala-Ala-Nap as substrates.

Animals↗
PubMed1980

Specificity of brain cathepsin D: cleavage of model peptides containing the susceptible Phe-Phe regions of myelin basic protein.

Brain cathepsin D, purified by affinity chromatography on Sepharose pepstatin columns, was incubated with synthetic peptides corresponding to the susceptible regions of the myelin basic protein encompassing the two Phe-Phe bonds. One peptide, Leu-Gly-Arg-Phe-Phe-Gly-Gly, was cleaved by cathepsin D at the Phe-Phe bond while another, Val-His-Phe-Phe-Lys-Asn-Gly, was resistant to cleavage. To determine if this was a result of His flanking the Phe-Phe bond, or chain length on the N-terminal side, two decapeptides were synthesized differing only in the presence or absence of His adjacent to Phe. The results show that both of the decapapetides were cleaved by cathepsin D at the Phe-Phe linkages. In addition, prolonged incubation led to release of N-terminal Lys, indicating an additional cleavage at the Phe-Lys bond. In contrast to the limited cleavage by cathepsin D, pepsin split all four peptides. These results support earlier work on the limited proteolysis of basic protein at the Phe-Phe bond and suggest additional sites upon prolonged exposure. Such peptides may have utility as alternative substrates for basic protein or as models for subsequent synthesis of possible inhibitors of the enzyme.

Amino Acid Sequence↗
PubMed1980

On the neurochemistry of an adult form of ceroid lipofuscinosis (Kuf's disease).

Little progress has been made in procedures for diagnosis of this baffling group of diseases known as ceroid lipofuscinoses (CL), which exhibit infantile, juvenile, and adult forms. Although these have been shown for the most part to be genetic in origin, the enzymatic or other defects leading to accumulation of lipopigments in tertiary lysosomes of neurons or astrocytes re unknown. Among the more commonly discussed theories is the role of peroxy radicals or their products formed by lipoperoxidation of polyunsaturated fatty acids. Although peroxy radicals are damaging to tissues and biological processes, no differences were observed in levels of leucocyte peroxidase (metabolizing H2O2) for Kuf's patients in comparison to age-matched controls. Also, no differences were observed in levels of blood factors that affect the rates of lipoperoxidatin by rat or human brain homogenates in vitro (measured by formation of MDA or other TBA positive materials).

Adult↗
PubMed1979

Mitigation of experimental allergic encephalomyelitis by cathepsin D inhibition.

Intraperitoneal treatment with the enzyme inhibitor, pepstatin, of BSVS mice, guinea pigs and Lewis rats which were sensitized with guinea pig spinal cord and pertussis vaccine resulted in complete or partial suppression of paralysis dependent on the species studied and alterations of histological signs of experimental allergic encephalomyelitis (EAE). The effect was dose-dependent but had no relationship to the age of the experimental animal at the time of the experiment.

Animals↗
PubMed1979

Degradation of luteinizing hormone-releasing hormone (LHRH) by brain prolyl endopeptidase with release of des-glycinamide LHRH and glycinamide.

A highly purified preparation of rabbit brain prolyl endopeptidase cleaved the decapeptide luteinizing hormone-releasing hormone (LHRH) at the ProGly . NH2 bond leading to the release within 1-3 h incubation at 37 degrees C of des-glycinamide LHRH and glycinamide. Evidence for this site of cleavage was obtained by the detection of glycinamide or glycine and groups by a microdanyslation procedure, and by separation of the breakdown products by high performance liquid chromatography (HPLC) on a revers phase C-18 column. Incubation led to the appearance of two new peaks as detected by HPLC one of which was collected and shown to have the composition consistent with des-glycinamide LHRH. The other peak ran in the position identical to that of authentic glycinamide. Results suggest that prolyl endopeptidase could play a role in the inactivation of LHRH in vivo.

Animals↗