What is involved to make a sound decision? Biochemistry is a scientific discipline; one that examines and interprets the foundational structures and functions of living systems. As with any judgment, as there are reasons for believing, there are also reasons for disbelieving, and the freely willed decision to choose which, should involve the discovery of truths to use as exemplars for seeking coherence and foundation to the premises that necessarily and sufficiently support the better argument f...
Mar 31, 2021•23 min
Annual Review of Cell and Developmental Biology Vol. 34:111-136 Journal of Neuroscience 23 October 2019, 39 (43) 8576-8583 Archivum Immunologiae et Therapiae Experimentalis 2013 Apr;61(2):119-25.
Mar 27, 2021•30 min
In this foundational lipid absorption lecture, Dr. Guerra address the roles of apo- lipoproteins, triacylglycerol and cholesteryl esters with membrane associated caveolae transport in adipocytes, endothelia and skeletal muscle. An Authentic Biochemistry Podcast Production. 25 March 2021.
Mar 25, 2021•30 min
Electron transport and the anapleurotics of intermediary metabolism. Dr. Daniel J. Guerra Authentic Biochemistry Studios 21.3.21
Mar 22, 2021•30 min
•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 microenvironments thus represent key elements in the development of the adaptive immune system. Consequently, impai...
Mar 21, 2021•30 min
•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 synthesis and also functions to control glycolytic vs. aerobic bioenergetic intermediary metabolic agency i...
Mar 19, 2021•30 min
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. Therefore, metabolic control over the severity of chronological age and the immunosenescence of the CNS can be ex...
Mar 16, 2021•29 min
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 aminotransferase (GABA-AT), which catalyzes the conversion of GABA to the excitatory neurotransmitter l-glutamic acid. T...
Mar 11, 2021•30 min
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 Published 9 March 2021 by Dr Daniel J. Guerra.
Mar 09, 2021•29 min
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 the hepatocyte cytoplasm and is ultimately excreted in urine. Glutaminase-1 (GLS1) is a mitochondrial ...
Mar 04, 2021•29 min
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 dehydrogenase and carbamoyl-P synthetase via discrete and potentiating ADP ribosylation and deacylation is ass...
Mar 02, 2021•30 min
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 activity of the urea cycle enzyme, carbamoyl phosphate synthase 1 (CPS1). SIRT5 mediated de-glutarylated CPS1...
Feb 26, 2021•30 min
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 multiple affinities of individual non-covalent binding interactions via enthalpy-driven catalysis. Lipoamidase activity of mitochondrial Sirtuin 4 ...
Feb 23, 2021•30 min
•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 ionsacross membrane (must consider electrical potential in addition to concentration difference): ∆ G = RT ln( C 2/ C 1) + ZF ∆ Y ( Z =charge of ion, F =Faraday’s constant, ∆ Y =membrane electrical potential in vol...
Feb 20, 2021•30 min
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.
Feb 20, 2021•20 min
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 authentic examples except on our planet. If life is contingent, where does it come from, how does it come about and why does it ex...
Feb 14, 2021•30 min
*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 for nutrient and oxygen supply, and resistance to anti-proliferative and apoptotic stimuli *In resting cells, the cell cycl...
Feb 11, 2021•30 min
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 levels of pro-inflammatory adipokines. Aging combined with chronic obesity not only promotes cardiovascular dis...
Feb 07, 2021•30 min
*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 acid/TAG, and pro- inflammatory cytokine production;they are released by adipocytes (e.g. leptin and a...
Feb 04, 2021•29 min
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.
Jan 28, 2021•30 min
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 neuropsycoses and anxiety disorders throughout life. Fear conditioning must be fluid to readjust according to reverse learning. Persisten...
Jan 25, 2021•30 min
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 an iterative decision response. In healthy environments, this variable tonicity is a readout for adaptation when goal-oriented beh...
Jan 21, 2021•29 min
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 process works in conjunction with the bilateral secondary somatosensory cortex (SII) process involved in execut...
Jan 20, 2021•29 min
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 STAT3 homodimers into the nucleus. This STAT3 homodimer binds to STAT-binding elements which promotes ...
Jan 17, 2021•28 min
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 Dysfunction Associated-Senescence (MiDAS) Senescence is a chronological and pathophysiological sequenced ev...
Jan 17, 2021•30 min
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 receptors, working memory is impaired while agentic focused attention becomes prominent so it seems...
Jan 14, 2021•29 min
• 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. dissatisfaction and defeat. • Stresses first become recognized in the developing fetus since the feta...
Jan 13, 2021•29 min
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 the organism for an appropriate response to various stressors such as physical trauma, insults to the...
Jan 10, 2021•30 min
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 oxidation to drive the ATP concentration to levels necessary to prepare for cell proliferation and evenbtua...
Jan 07, 2021•29 min
There is a requirement of cholesterol and ceramides for the maintenance of neuronal and T cell porosome integrity, accompanying an interaction of phosphatidic acid (PA) and polyphosphoinositide (PI) lipids with syntaxin-1A where these lipids are necessary for neurotransmitter or cytokine secretion in association with calcium channels modulated by lipid domain formation upon sphingomelinase and fatty acyltransferase activities. Complex lipid composition and three dimensional sequence topology dif...
Jan 06, 2021•29 min
