Celiac Disease in Infancy and Childhood
Tadeusz P. Chorzelski, Ernst H. Beutner, Vijay Kumar, Tadeusz K. Zalewski in Serologic Diagnosis of Celiac Disease, 2020
In addition to the immunological theories, a number of hypotheses have been advanced which invoke either abnormal intestinal epithelial cell metabolism or structure for the pathogenesis of celiac disease. Although it has been difficult to disprove these theories, evidence to support them has not accumulated in recent years. The earliest theory was that of Frazier et al.,30 who raised the “missing peptidase” hypothesis. The congenital absence of this peptidase would result in the maldigestion of gluten with accumulation of harmful peptides. This view has not been substantiated, since several authors have demonstrated that the pattern of gliadin digestion by celiac mucosa is essentially unchanged.8,13,17,72 The previously suspected primary lack of glu-tamyltranspeptidase could not be confirmed, since Zalewski et al.83 found an increase of the glutamyltranspeptidase in recovered celiac mucosa.
Intracellular Peptide Turnover: Properties and Physiological Significance of the Major Peptide Hydrolases of Brain Cytosol
Gerard O’Cuinn in Metabolism of Brain Peptides, 2020
It now appears that these three originally defined activities are directed toward oligopeptide substrates and not proteins. A fourth recently described activity termed “caseinolytic” is likely to be responsible for the initial degradation of proteins. Chemical modification of the complex discriminates peptidase and proteinase activities. Thus N-acetylimidazole, a mild acetylating agent, inhibits the trypsinlike and peptidyl-glutamylpeptide hydrolyzing activities while stimulating the degradation of β-casein21. 3,4-dichloroisocoumarin, a mechanism-based serine proteinase inhibitor, inhibits all three activities while markedly activating the hydrolysis of β-casein22. At present the exact number of distinct catalytic components within the complex is not known and evidence for still other activities has been presented23,24. It is likely that all activities act in concert to efficiently degrade proteins to small peptide products. A mechanism whereby intermediates arising from the degradation of proteins are efficiently channeled between different catalytic centers has been proposed25.
Macromolecular Absorption From The Digestive Tract In Young Vertebrates
Károly Baintner in Intestinal Absorption of Macromolecules and Immune Transmission from Mother to Young, 2019
The newborn piglet absorbs amino acids already in the early postnatal life. These are mainly colostral free amino acids on the first day and amino acids derived from milk proteins thereafter.107 The free amino acids absorbed leave the circulation rapidly and are used or metabolized in the tissues.513,1146 The small peptides behave similarly, due to their degradation to amino acids by extra- and intracellular peptidases. In contrast, intact IgG does not enter the cells of extraintestinal tissues, but is retained in the extracellular compartment with a 1.0:1.2 distribution between intra- and extravascular spaces in the calf.943 The 19S IgM persists in the intravascular space somewhat longer than the 7S IgG. Antibodies also appear in the synovial fluid of the calf,1380 although little IgG penetrates into the synovial space of the adult cow.
Metataxonomic and metaproteomic profiling of the oral microbiome in oral lichen planus - a pilot study
Published in Journal of Oral Microbiology, 2023
Maria Bankvall, Miguel Carda-Diéguez, Alex Mira, Anders Karlsson, Bengt Hasséus, Roger Karlsson, Jairo Robledo-Sierra
To identify putative protein biomarkers in OLP lesions, we used mass spectrometry to detect the bacterial proteins expressed in our samples and compare their presence between affected and non-affected oral mucosa of patients with OLP. Consequently, peptides were annotated using a protein database based on the Human Oral Microbial Database (Supplementary Table S1), confirming the presence of bacteria identified by 16S rRNA sequencing. Most peptides corresponded to basic metabolic functions such as the 30S and 50S ribosomal subunits, DNA/RNA metabolism, or ABC transporters. Other peptides were annotated as hypothetical proteins, and their annotation could not be refined. Several peptides were putatively annotated as belonging to G. haemolysans, previously detected by our 16S rRNA analysis as a potential OLP biomarker. Also, many peptidases were found in the proteome data, potentially having a virulence function (Supplementary Table S2). Interestingly, some bacteria associated with the OLP group were identified in the metaproteome that were not amplified by the 16S rRNA gene sequencing approach, including the pathogen Mycoplasma fermentans.
Murepavadin: a new antibiotic class in the pipeline
Published in Expert Review of Anti-infective Therapy, 2018
Ignacio Martin-Loeches, Glenn E. Dale, Antoni Torres
It is well established that therapeutic peptides are typically eliminated by proteolytic degradation, with the resulting amino acids incorporated into the endogenous pool. Proteases and peptidases are ubiquitous throughout the body, particularly in the blood, liver, kidney, and small intestine. Therefore, degradation of many peptides in vivo is rapid, with t1/2 as short as 10 min [46]. Cyclization of a peptide chain and inclusion of D-amino acids can limit the effect of endogenous proteases [47], which may in part explain the longer t1/2 of 5–8 h of murepavadin in humans. Metabolism of murepavadin was studied in mouse, rat, monkey and man [48]. While in mouse, monkey, and man the initial ring opening of the intact molecule preferentially occurs at the A-S bond of the circular peptide, rat seems to process the molecule differently (i.e. initial cleavage at two additional sites: W-I and W-Dab bond).
Cerliponase alfa for CLN2 disease, a promising therapy
Published in Expert Opinion on Orphan Drugs, 2020
Shawn C. Aylward, Jonathan Pindrik, Nicolas J. Abreu, W. Bruce Cherny, Matthew O’Neal, Emily de Los Reyes
Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a subtype of the collective family of neuronal ceroid lipofuscinosis or Batten’s disease. CLN2 is an ultra-rare autosomal recessive disorder occurring in 0.15 to 9.0 per 100,000 live births [1]. The disorder is caused by biallelic pathogenic variants in the gene encoding for the lysosomal enzyme tripeptidyl peptidase (TPP1), which is located on chromosome 11p15 [2,3]. This enzyme is activated within cellular lysosomes to allow protein cleavage into tripeptides. Lack or reduced effectiveness of this enzyme results in accumulation of autofluorescent ceroid lipofuscin in the intracellular space of neurons and other tissues. Over time, this accumulation results in progressive neuronal degeneration [2].