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Artwork for Authentic Biochemistry
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Authentic Biochemistry

Dr Daniel J. Guerra

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  • Mar 19, 2021 · 29 min

    ADP- Glucokinase is essential for T lymphocyte activation and pro-inflammatory cytokine synthesis and secretion. DJGPhD. 19.3.21

    •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 in lymphocytes. Scientific Reports volume 9, Article number: 14248 (2019)

  • Mar 16, 2021 · 29 min

    The control of C flux in the liver, pancreas and CNS are coordinated: Potential Axis for Immuno Senescence X Intermediary Metabolic Regulation.Authentic Biochemistry . 15 March 2021. DJG PhD.

    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 exacerbated by visceral obesity thus linking CNS decline to the major causes of morbidity and mortality in the aging human population. Curr Opin Lipidol. 2015 Apr; 26(2): 88–95 Am J Physiol Endocrinol Metab. 2016 Jul 1; 311(1): E42–E55

  • Mar 11, 2021 · 29 min

    The pyridoxal phosphate contribution to amino acid metabolism and neurotransmitter turnover Dr Guerra Authentic Biochemistry 10 March 2021

    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. Trends in Cell Biology 2020. 30.6: 440-451. Chem. Rev. 2018. 118. 7: 4037–4070

  • Mar 9, 2021 · 29 min

    Reactive Oxygen and the gamma-glutamyl cycle for GSH redox biochemistry and the prolegomena of neurodegeneration. DJGPhD 09March21'

    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 4, 2021 · 29 min

    Deacylation regulation of amino acid catabolism as a source of multiple bioenergetic and discrete excitotoxicity phenomena. DJGPhD . 03March2021

    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 enzyme found in endothelial cells (ECs) that metabolizes glutamine to glutamate and ammonia and glutaminolysis modulates the function of human umbilical vein endothelia.Glutamine deprivation or GLS1 inhibition also stimulated the production of reactive oxygen species and this was associated with a marked decline in heme oxygenase-1 (HO-1) expression. GLS1 inhibition also sensitized umbilical endothelia to the cytotoxic effect of hydrogen peroxide; a process that is blocked by the overexpression of Heme oxygenase 1. In summary, GLS1 promotes human endothelial proliferation, migration, and survival. SIRT4 might prevent CNS excitotoxicity and subsequent apoptosis by reducing glutamine synthesis while and upregulating glutamate transport into astrocytes where increased glutamate dehydrogenase activity removes the ultimate source of this neural degeneration mechanism. In the small intestine, SIRT5 causes deglutarylation and functional activation of glutamate dehydrogenase 1 leading to poor prognosis in colorectal cancer. Combined, this experimental evidence suggests that the modulation of mitochondrial Sirtuin activity to pharmacologically circumvent CNS pathophysiology may not be appropriate for cancers in the digestive system and that Sirtuin isoform expression and activity is highly nuanced. J Cell Mol Med. 2017 Sep; 21(9): 2036–2045 Hum Exp Toxicol. 2020 Jul;39(7):938-947

  • Mar 2, 2021 · 29 min

    Amino Acid Catabolism via Sirtuins Modulation and the Redirecting of Hepatic and Intestinal Intermediary Metabolism. Dr Guerra Authentic Biochemistry. 02 March 2021

    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 associated with pancreatic insulin secretion, hepatic amino acid utilization and the potential for pathobiochemical sequalae

  • Feb 26, 2021 · 29 min

    Sirtuins obtain a significant role in mitochondrial metabolism linked to caloric restriction and cancer. Dr Guerra. Authentic Biochemistry.26.02.21

    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 is elevated in activity to maintain urea cycle competency during active amino acid incorporation into the bioenergetic machinery thus promoting the potentiation of tumorigenesis. Science. 2011 Nov11; 334(6057): 806–809 Cell Metab 2014 Apr 1;19(4):605-17. Nat Commun. 2018 Feb7;9(1):545 Cell. 2006 Sep 8;126(5):941-54 Mol Cell. 2013 Jun 6; 50(5): 686–698

  • Feb 23, 2021 · 29 min

    Thermodynamics and regulation involving lipoic acid biochemistry of the classical 2-oxo acid dehydrogenase complexes. Dr Guerra 23.02.2021

    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 modulates cellular fate by generating a debilitating removal of PDH-E2 dihydrolipoyllysine acetyltransferase-bound lipoic acid thus driving glutaminolysis over glucose oxidation. Cell. 2014 Dec 18; 159(7): 1615–1625. PNAS | August 23, 2016 | vol. 113 | no. 34 Structure VOLUME 13, ISSUE 8, P1119-1130, AUGUST 01, 2005

  • Feb 20, 2021 · 29 min

    Physical Biochemistry of Free Energy Transfer for Membrane Transport of Molecules and Ions.Dr Dan Guerra 19 Feb 2021

    •Free energy change(chemical potential difference) for transporting 1 mole of a substance from region where its concentration is C1 (e.g., Cout) to region where its concentration is C2 (e.g., Cin): ∆G= RTln(C2/C1) (favorable with ∆G< 0 if C2< C1) •Transport of ionsacross membrane (must consider electrical potential in addition to concentration difference): ∆G= RTln(C2/C1) + ZF ∆Y (Z=charge of ion, F=Faraday’s constant, ∆Y=membrane electrical potential in volts) •Coupled transport (active transport): ∆G= RTln(C2/C1) + ∆G´ (∆G´ of coupled process, such as ATP hydrolysis, may be negative enough to compensate for unfavorable transport against concentration gradient when RT ln (C2/C1) > 0) •Diffusional transport: movement of substance from high to low concentration across membrane (down concentration gradient) –Non-facilitated diffusion across lipid bilayer (slow for most biological substances) –Facilitated diffusion (accelerated diffusion by making membrane more permeable to specific transported substance, e.g., channels and carriers) •Active transport: Actively driven (generally directly or indirectly coupled to ATP hydrolysis) transport against concentration gradient from low to high concentration across membrane (e.g., pumps)

  • Feb 20, 2021 · 19 min

    Membrane Proteins 1 Mini Lecture Dr Guerra 19 Feb 2021

    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 14, 2021 · 29 min

    Application of the Principle of Sufficient Reason to Biochemical Thermodynamics. Dr Dan Guerra 13 February 2021

    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 exist? You see where this is going. Why is there a physical universe? Why isn’t there just nothingness? Answering with the typical “it just is!” only further confounds the question. The word “just” here, operates syntactically with contingency. By that I mean, proposing that the modality of an event, life in this context, simply "is" a state function, makes no claim that the event "must be". And so…we are back to the beginning. A beginning that has no source. The Big Bang could be such a beginning, but then again, some event had to proceed it , even if time itself had this event as its source. As a biochemist I authentically and humbly do not obtain sufficient reason to obtain life from the non-living and so I will to be content, on finding how biochemical events happen. As an existing individual, I believe in God.

  • Feb 11, 2021 · 29 min

    Cell Cycle kinase inhibition may improve healthy cardiac aging while promoting global tumorigenesis. Authentic Biochemistry 10Feb2021 by Dr Guerra.

    *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 cycle is strictly managed by a set of regulatory proteins that control the various cell cycle checkpoints and this will become dysfunction during the early transforming stage of the tumorigenesis via the unregulated dismantling of tumor suppressor genes *Suppression is the programmed deliberative inhibition of biochemical events while repression is the unintentional inhibition of biochemical events *When a biochemical event is de-repressed it is brought back to register, regardless of valence *In effect this dismantling is a repression of tumor suppressor gene transcription and/or translation, post-translational modifications or final agency *This loss of gene suppressor “activity” can result from deletion, inactivating mutations, epigenetic silencing, incoherent post-translational modification(s) including glycosylation/acylation/prenylation/phosphorylation/aggregation etc.or lipid mediated transport aberrations as with membrane lipid rafts from Sphingomyelinase mediated ceramide synthesis. *The typical biomedical result is oncogenesis(transformative) and ultimately tumorigenesis (committed), metastasis (mobilized and transactional) and either death or repair to healthy state. *The progression of the mammalian cell cycle from G1 to mitosis is regulated by cyclins with their cogent catalytic subunits, the referred to as cyclin-dependent kinases (CDKs) *A family of cyclin–CDK inhibitor proteins (CDIs), which bind and inactivate the CDKs, includes the p16INK4a, p21CIP1, p27KIP1, and associated proteins p15INK4b, p18INK4c, p19INK4d and p57KIP2 *These proteins potentially act as tumor suppressors and their inactivation corresponds with human carcinogenesis. *Selective removal of CDK inhibitors may ablate senescent cell lineages in a process known as senolysis which may promote healthy cardiac muscle aging in the elderly * In balance the square of opposition logical conclusion is to distinguish between contrarion vs. contradictory physiological and pharmaco-therapies. Dr Daniel J. Guerra Authentic Biochemistry Published on 10 February 2021 Refs EBioMedicine 2016 830-39DOI: (10.1016) BMC Cancer volume 20, Article number: 882 (2020) J Cardiol. 2019 Oct;74(4):313-319 Front. Neurosci., 24 July 2019 | https://doi.org/10.3389/fnins.2019.00728

  • Feb 7, 2021 · 29 min

    Adipokine Update Lecture 2. Authentic Biochemistry Podcast. Dr. Dan Guerra Published 06 Feb 2021

    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 disease and cancer but further promotes autoimmune disease, dementia and high morbidity metabolic dysfunction, respiratory disease, and hyperimmune response to otherwise non-virulent pathogens linked to mortality. International Scholarly Research Notices, vol. 2013, Article ID 139239, 12 pages, 2013. https://doi.org/10.1155/2013/139239

  • Feb 4, 2021 · 29 min

    Adipokine Mini Review I Daniel J. Guerra, PhD. 03 Feb 2021 Authentic Biochemistry Podcast Publications.

    *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 adiponectin) or preadipocytes, adipose tissue-infiltrated immune cells, or the gastric system Indeed, Th2 lymphocytes promote adipose glucose homeostasis by enhancing insulin sensitivity in adipocytes and browning/brown adipose tissue (BAT) activation but chronic inflammation of white adipose tissue (WAT) leads to the activation of pro-inflammatory pathways in adipocytes and resident immune cells following obesity involving the shutting down of Tregs and anti-inflammatory cytokines. Front Physiol. 2020; 11: 578966 Indian J Pharmacol. 2012 Mar-Apr; 44(2): 155–156. Cells. 2019 Mar; 8(3): 227.

  • Jan 25, 2021 · 29 min

    Neuropeptide Y and the fear conditioning response: are aging and obesity prodromal to anxiety and cognitive decline? Daniel J. Guerra PhD. Published 25 January 2021

    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. Persistent fear and avoidance of the potential for fear-associated events are common presentations of social anxiety disorder (SAD) and avoidant behavior maintains SAD, thus it prevents the reversal of fear in social situations. The best treatment outcomes are CBT including exposure therapy, which leads to fear extinction. Pharmacotherapy including antidepressants, benzodiazepines, beta-blockers, anticonvulsants, or neuroleptics, are commonly administered with low efficacy. Neuropeptide Y (NPY), a 36-amino acid peptide, is the most abundant and widely distributed neuropeptide in the mammalian brain and it may be involved in social behavior and the fear circuitry, including activities in the amygdala, hippocampus, septum, periaqueductal gray, locus coeruleus, cerebral cortex, basal ganglia, hypothalamus, and thalamus. NPY is also a feeding simulant, regulator of blood pressure, bioenergetics , neuroendocrine hormone responses, neuronal excitability, and neuroplasticity including epigenetic mechanisms. Not surprisingly, exogenous NPY causes a variety of behavioral effects when administered into the brain of rodents including stimulation of food intake when administered into the hypothalamic paraventricular nucleus, and it promotes social interaction when administered into the dorsolateral septum and basolateral amygdala and has anxiolytic and antidepressant-like effects when administered intracerebroventricularly (i.c.v.).NPY also affects different aspects of fear-related behaviors, as shown in fear conditioning studies in rodents. Next time we will link Acid Sphingomyelinase to NPY and the anxiety disorders of the elderly.. Int J Mol Sci. 2020 Nov; 21(21): 8220.

  • Jan 21, 2021 · 29 min

    Corticotropin Releasing Factor and the Monoamine Fear Response in Aging. Sequence II. The reverse learning scenario as cognitive redistribution of neural transmission valency. DJGPhD.21.01.2021.

    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 behavior is relaxed so that the individual uses pro-forma decisions even when novel environmental stimuli are encountered. During aging these pathways lose flexibility due to a decrease in executive decision making linked to the senescence phenotype that may impair neural circuitry via inflammation, over or under activation and lack of control over immune cell responses. J Neurosci. 2008 Nov 5; 28(45): 11517–11525. GeroScience. 2017 Feb; 39(1): 61–72. Neuroscience. 2017 Mar 14; 345: 12–26.

  • Jan 20, 2021 · 28 min

    The Corticotropin Releasing Factor and the Somatosensory Catecholamine Circuit in ExtraDimensional (attentional) Shifting. Dr Guerra 20 Jan 2021.AB.

    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 executive decision making. Where stimulated, the primary sensory motor-neuronal process is integrated with novel extra-dimensional learning . Recall that this fear stress response can lose functional valency upon immune-regulating, senescent secretory phenotypes. In the aging brain, where CRF axon terminals are widely distributed, (including within catecholamine and serotonin nuclei) there are widespread cortical projections into the medial prefrontal cortex; linking executive functional responses to adverse stimuli. Dr. Daniel J. Guerra Authentic Biochemistry Published 20 Jan 2021 Refs Neuroimage. 2008 May 1;40(4):1765-71. Biol Psychiatry. 2009 Sep 15; 66(6): 586–593.

  • Jan 17, 2021 · 27 min

    Aging-associated SASP vs. MiDAS is a contrarion trade-off that may lead to neurodegeneration and autoinflammation vs tumorigenesis and heart disease respectively. Dr. Dan Guerra.17 Jan 2021. AB

    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 the expression of the suppressor of cytokine signaling 3 (SOCS-3) and IL-1 receptor antagonist (IL-1RN). IL-10 reduces the production of pro-inflammatory cytokines (IL-1β, IL-6, tumor necrosis factor alpha) and diminished expression of both major histocompatibility complex II. The anti-inflammatory MiDAS phenotype can also induce heart failure in the aging population. References: Front Pharmacol. 2019; 10: 200 Aging Cell. 2018 Oct;17(5) Int Heart J. 2018 Jul 31;59(4):837-844 Front. Immunol., 19 March 2018 Neuro Oncol . 2020 Mar 5;22(3):333-344

  • Jan 17, 2021 · 29 min

    An Immunological Distinction between Senescence linked Secretory Phenotypes: SASP vs. Midas. Dr. Dan Guerra. Authentic Biochemistry 16 Jan 2021

    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 event response that restricts mitotic division and thus aberrant proliferation of damaged, infected and/or tumor inducing cells. Because these cells are senescent and exhibit low anabolic currency to present self-produced antigen epitopes as displayed by HLA, they are not targeted by immune responses but rather, may become secretory and induce inflammation by instantiating the Senescence Associated Secretory Phenotype-SASP. Senescence presents with metabolic reprogramming, epigenetic chromatin remodeling, and the secretion of growth factors, signaling molecules, proinflammatory cytokines and chemokines, extra-cellular matrix metallo proteases, nucleotides, exosomes and ionic bursts collectively referred to as SASP. Both SASP and MiDAS can occur in the CNS during human aging thus generating a remarkably complex-contrarion dual pathophysiological phenotype leading to neurodegeneration or more rarely, certain forms of brain cancer. Authentic Biochemistry Podcast is produced by Daniel J. Guerra, PhD. Today's Date: 16 January 2021 Refs. Trends in Biochemical Sciences Volume 41 Issue 3 Pages 207-209 (March 2016) Cell Metabolism Volume 23, Issue 2, 9 February 2016, Pages 303-314 Front. Immunol., 19 March 2018