Collagen Racemization and Deposition in the Lungs of Aged Rats

Kasai, Akiko; Yamashita, Naomi; Utsunomiya‐Tate, Naoko

doi:10.4137/bci.s4210

Cited by 5 publications

(5 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is a need for reliable techniques to screen for DNA preservation prior to destructive sampling. An increase in amino acid racemization has been linked with age, − and aspartic acid racemization has been successful in forensic age estimation when the postmortem interval is relatively short. , The extent of aspartic acid racemization (AAR) was thought to be a good measure of the likelihood of DNA survival, but Collins et al found no correlation between the extent of AAR and DNA amplification success and conclude that amino acid racemization is not a useful screening technique for ancient DNA from bone …”

Section: Discussionmentioning

confidence: 99%

Assessing the Extent of Bone Degradation Using Glutamine Deamidation in Collagen

2012

View full text Add to dashboard Cite

Collagen peptides are analyzed using a low-cost, high-throughput method for assessing deamidation using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). For each chosen peptide, the theoretical distribution is calculated and the measured distribution for each sample compared with this to determine the extent of glutamine deamidation. The deamidation of glutamine (Q) to glutamic acid (E) results in a mass shift of +0.984 Da. Thus, from the resolution of our data, the second peak in the isotope distribution for a peptide containing one glutamine residue coincides with the first peak of the isotope distribution for the peptide in which the residue is deamidated. A genetic algorithm is used to determine the extent of deamidation that gives the best fit to the measured distribution. The method can be extended to peptides containing more than one glutamine residue. The extent of protein degradation assessed in this way could be used, for example, to assess the damage of collagen, and screen samples for radiocarbon dating and DNA analysis.

show abstract

Section: Discussionmentioning

confidence: 99%

Assessing the Extent of Bone Degradation Using Glutamine Deamidation in Collagen

2012

View full text Add to dashboard Cite

show abstract

“…Another part of PTMs Sp is known to disrupt the natural course of molecular events, often leading to pathogenic misfolding, malfunction, and aggregation of proteins. One of the most studied forms of pathogenic reactions is racemization [ 69 , 70 ]. As an unavoidable consequence of pathogenic PTMs, we can expect that even small (limited only to one or two AAs) racemization can trigger the deviation from the NS.…”

Section: Biological Language Of Protein Conformationmentioning

confidence: 99%

Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality

Dyakin

Uversky

2022

IJMS

View full text Add to dashboard Cite

Chirality is a universal phenomenon, embracing the space–time domains of non-organic and organic nature. The biological time arrow, evident in the aging of proteins and organisms, should be linked to the prevalent biomolecular chirality. This hypothesis drives our exploration of protein aging, in relation to the biological aging of an organism. Recent advances in the chirality discrimination methods and theoretical considerations of the non-equilibrium thermodynamics clarify the fundamental issues, concerning the biphasic, alternative, and stepwise changes in the conformational entropy associated with protein folding. Living cells represent open, non-equilibrium, self-organizing, and dissipative systems. The non-equilibrium thermodynamics of cell biology are determined by utilizing the energy stored, transferred, and released, via adenosine triphosphate (ATP). At the protein level, the synthesis of a homochiral polypeptide chain of L-amino acids (L-AAs) represents the first state in the evolution of the dynamic non-equilibrium state of the system. At the next step the non-equilibrium state of a protein-centric system is supported and amended by a broad set of posttranslational modifications (PTMs). The enzymatic phosphorylation, being the most abundant and ATP-driven form of PTMs, illustrates the principal significance of the energy-coupling, in maintaining and reshaping the system. However, the physiological functions of phosphorylation are under the permanent risk of being compromised by spontaneous racemization. Therefore, the major distinct steps in protein-centric aging include the biosynthesis of a polypeptide chain, protein folding assisted by the system of PTMs, and age-dependent spontaneous protein racemization and degradation. To the best of our knowledge, we are the first to pay attention to the biphasic, alternative, and stepwise changes in the conformational entropy of protein folding. The broader view on protein folding, including the impact of spontaneous racemization, will help in the goal-oriented experimental design in the field of chiral proteomics.

show abstract

“…d-Ser is known to be involved in glutamate transmission and plays a role in long-term potentiation [ 378 ]. D-AAs found in many AD-related proteins including neuronal-specific neurofilament-L [ 379 ], MBP [ 56 ], and in protein phosphatase PPC1 [ 380 , 381 ]. PPC1 and PPC2 are involved in TAU de-phosphorylation at multiple serine/threonine sites [ 382 , 383 ].…”

Section: Racemization Role At Molecular Cellular and System (Organ) Levelsmentioning

confidence: 99%

Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip of the Iceberg

2021

View full text Add to dashboard Cite

Homochirality of DNA and prevalent chirality of free and protein-bound amino acids in a living organism represents the challenge for modern biochemistry and neuroscience. The idea of an association between age-related disease, neurodegeneration, and racemization originated from the studies of fossils and cataract disease. Under the pressure of new results, this concept has a broader significance linking protein folding, aggregation, and disfunction to an organism’s cognitive and behavioral functions. The integrity of cognitive function is provided by a delicate balance between the evolutionarily imposed molecular homo-chirality and the epigenetic/developmental impact of spontaneous and enzymatic racemization. The chirality of amino acids is the crucial player in the modulation the structure and function of proteins, lipids, and DNA. The collapse of homochirality by racemization is the result of the conformational phase transition. The racemization of protein-bound amino acids (spontaneous and enzymatic) occurs through thermal activation over the energy barrier or by the tunnel transfer effect under the energy barrier. The phase transition is achieved through the intermediate state, where the chirality of alpha carbon vanished. From a thermodynamic consideration, the system in the homo-chiral (single enantiomeric) state is characterized by a decreased level of entropy. The oscillating protein chirality is suggesting its distinct significance in the neurotransmission and flow of perceptual information, adaptive associative learning, and cognitive laterality. The common pathological hallmarks of neurodegenerative disorders include protein misfolding, aging, and the deposition of protease-resistant protein aggregates. Each of the landmarks is influenced by racemization. The brain region, cell type, and age-dependent racemization critically influence the functions of many intracellular, membrane-bound, and extracellular proteins including amyloid precursor protein (APP), TAU, PrP, Huntingtin, α-synuclein, myelin basic protein (MBP), and collagen. The amyloid cascade hypothesis in Alzheimer’s disease (AD) coexists with the failure of amyloid beta (Aβ) targeting drug therapy. According to our view, racemization should be considered as a critical factor of protein conformation with the potential for inducing order, disorder, misfolding, aggregation, toxicity, and malfunctions.

show abstract

Collagen Racemization and Deposition in the Lungs of Aged Rats

Cited by 5 publications

References 55 publications

Assessing the Extent of Bone Degradation Using Glutamine Deamidation in Collagen

Assessing the Extent of Bone Degradation Using Glutamine Deamidation in Collagen

Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality

Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip of the Iceberg

Contact Info

Product

Resources

About