Authentic Biochemistry

•Impaired immunological responsiveness is common in the elderly •The immunological competence of an individual is determined by the presence of mature lymphocytes formed in primary lymphoid organs, and secondary lymphoid tissues such as the liver, lung and GI tract. •Immunological equilibrium requires steady lymphocyte output, and controlled expansion •Thymic and lymph-node stromal microenvironmen...

•Cytokines regulate the intensity and duration of the immune response, and  they can act as growth factors or stimulants or even inhibitors of T cell amplification and differentiation. •Cytokines are glycoproteins that are synthesized through a dolichol PP mediated pathway in the ER and are thus dependent upon prenyl lipid metabolism Endoplasmic reticulum localized ADPGK serves glycoprotein s...

1. Glucokinase- GK is in the neuron 2.Control over glycolysis via GK mediates neural transmission 3.  Neuronal GK further functions on  the appetite/satiety axis thus partially regulating the HPA axis 4. Aging and immune associated dysfunction of these glycolytic systems are associated with neurodegeneration and the loss of neuronal action potential mediated learning, memory, and mood. T...

If  γ-aminobutyric acid (GABA) concentration drops significantly in the synaptic cleft, excitotoxicity can obtain, sometimes presenting with epileptic convulsions. This can be reversed by decreasing the concentration of L-glutamate via control over the activity of glutamate dehydrogenase, glutamine synthetase and glutamate transporters or by  the inhibition of  γ-aminobutyric acid a...

A basic lecture on reactive oxygen synthesis and reduction coupled with glutathione, folic acid and amino acid metabolism. This lecture is foundational for subsequent synthesis with neural transmission, microglial activation and exicitotoxicity leading to neurodegeneration in the aging human CNS. Please subscribe, rate and review, and  contribute to Authentic Biochemistry! djgphd@gmail.com Pu...

CPS-1 activity is regulated by liver enriched transcription factors as well as Sirtuin-mediated de-acylation. Glutaminase breaks down glutamine into glutamate and ammonia. Glutamate also yields additional NH4+ via the enzyme glutamate dehydrogenase. From here, ammonia is initially incorporated into hepatocyte mitochondria and ultimately results in the formation of urea. Urea subsequently leaves th...

Glutaminase breaks down glutamine into glutamate and ammonia. Glutamate also yields additional urea via the enzyme glutamate dehydrogenase. From here, ammonia is initially incorporated into hepatocyte mitochondria and ultimately results in the formation of urea. Urea subsequently leaves the hepatocyte cytoplasm and is ultimately excreted in urine. Sirtuin mediated control over glutamate dehydrogen...

SIRT5 causes deglutarylation and functional activation of glutamate dehydrogenase 1  which is  essential to cellular glutaminolysis. Indeed, SIRT5 supports the anaplerotic transamination entry of glutamine and other amino acids as alpho ketoglutarate into the TCA cycle in malignant phenotypes of colorectal cancer via activation of the glutamate dehydrogenase1. Sirt5 is known to regulate...

The Pyruvate dehydrogenase hydrated E1-E2 interface is  enthalpy driven, while the dehydrated  E3-peripheral subunit binding domain complex is driven by entropy obtaining a favourable  delta G= delta H-T delta S=  -33.4kj mol where the domain interfacial hydration obtains surface  thermal complementarity  and contributes finally to an aggregate  strength of multi...

• Free energy change (chemical potential difference) for transporting 1 mole of a substance from region where its concentration is C 1 ( e.g. , C out) to region where its concentration is C 2 ( e.g. , C in): ∆ G = RT ln( C 2/ C 1) (favorable with ∆ G < 0 if C 2< C 1) • Transport of ions across membrane (must consider electrical potential in addition to concentration difference): ∆ G = RT ln(...

Mini Lecture 1 on Membrane Physiological Biochemistry. The amino acid sequence of membrane associated polypeptides obtains secondary structure, glycosylation, acylation and hydropathy which confer functionality (in part) by targeting specific membrane domains.

For Valentine's Day Eve. A bouquet assortment of  biochemical  thermodynamic principles and  metaphysical event ontologies. To finish my thoughts:  Is life necessary? How to answer this question? One way is to ask if there is sufficient reason for its existence. Outside of spiritual or theological discussion, the answer is compellingly obscure especially since we find no authen...

*Oncogenesis eventuates genetic mutation to epigenetic gene expression mechanisms with molecular signatures either inappropriately proscribed, incorrectly prescribed upon writing as  dangerous and deleterious, or erasure;  leaving a corrupted  chromatin result.  *Tumor cells obtain proliferative autonomy, autophagous –self-maintenance in growth and signaling, neovascularization...

Intra abdominal adiposity (IAA)  linked obesity may be the most significant contributory factor to high mortality human disease after aging. IAA  presents with systemic and chronic inflammation and enlarged White Adipose Tissue (WAT) adipocytes that have been infiltrated with lymphocytes and macrophages that secrete pro-inflammatory cytokines, chemokines, growth factors and inappropriate...

*Adipose tissue is the endocrine organ that secretes “adipokines” *Nothing new to the Authentic Biochemistry crew; adipokines have been very well discussed here and their function as mediators of the feeding/appetitive/satiety response through the arcuate nucleus of the hypothalamus (POMCvNPY neurons) was most recently addressed. *Adipokines mediate the BMI, heart rate, serum glucose &fatty ac...

Proceedings of The Nutrition Society.2012 71(4):521-33 Autophagy. 2009 May; 5(4): 558–560 Molecular and Cellular Endocrinology Volume 472, 5 September 2018, Pages 40-49 Int J Mol Sci. 2020 Nov; 21(21): 8220.

Fear-conditioning  learning is a low-threshold  enduring psychiatric  process that prepares a defense against dangerous phenomena and reduces the need to iteratively  relearn the signal. It is a pattern recognition response that can be modulated by experience and the severity of the stress signal and it is  a response that deteriorates in the elderly and in certain neurops...

Homeostatic  chronic  low stress results in low to moderate levels of CRF in the LC in association with  enhanced Extra-Dimensional Shifting and optimal executive decision making. However, acute or chronic severe stress is linked to  high levels of CRF in the LC and this may  contribute to a shift from optimal executive function necessary for goal-directed behavior toward...

Adaptation to stress-such as the fear response obtains dopaminergic input to striatum and prefrontal cortex and  is thought to signal unexpected events and facilitate a shift in attention to promote new learning within the contralateral primary somatosensory cortex (SI) which has been associated with the agentic categories of both the quality and quantity of thought event ontology. This proce...

The anti-inflammatory IL-10 pathway in the CNS can lead to Glioblastoma which is a disease presented 3-4 fold higher in people ≥65 years old, and with a mortality rate for the same age group some 7 fold higher. Activation of the IL-10 Receptor bound ligand induces the JAK1 signal transducer and activator of transcription 3 (STAT3) pathway in APCs. This results in the subsequent translocation of ST...

Non-uniform ageing is a major associative risk factor for cancer and degenerative diseases and mitochondrial dysfunction is linked to cellular senescence in association with cell cycle arrest, telomerase decline and nucleic acid/lipid/protein oxidation. Indeed, mitochondrial dysfunction comprises a distinct type of cellular senescence; mitochondrial SIRT3 or SIRT5, can induce Mitochondrial Dysfunc...

LC axonal projections to the mPFC modulate a diversity of cognitive processes, including working memory, sustained attention, and flexible attention and under moderate rates of LC activity and NE release, high-affinity postsvnaptic α2 adrenergic receptors in the PFC are preferentially engaged and promote working memory However, with elevated LC firing and activation of lower affinity α1 adrenergic...

• Intensive and chronic or excessive stress diminishes intellectual performance and general cognition: this is a form of negative reinforcement and can be related to learning disability and anxiety about future events. Indeed, • Individual responses and the magnitude of stressor as well as its association with self identity and goals will influence endurance, resilience, and self-empowerment vs. d...

1. Corticotropin releasing factor (CRF) or hormone (CRH) is one of several neurohormones synthesized by specific hypothalamic nuclei in the brain and released into the portal system which bathes the anterior pituitary 2. CRF has marked CNS effects by acting at higher centers in the brain: cortical regions where there is a widespread distribution of CRF neurons. 3. Major role of CRF is to prepare t...

Naïve T Cell metabolic regulationinvolves allosteric and kinetic mechanisms for maximum capacity to switch from glucose uptake to fatty acylCoA utilization for bioenergetic demand. Multiple mechanisms of this coordinated regulation involve the fatty acyl CoA concentration modulation by fine tuning cyctosolic fatty acid synthesis from glucose or lactate or amino acids vs. mitochondrial  beta o...