Explore chapters and articles related to this topic
Clinical Manifestation of Mitochondrial Disorders in Childhood
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Mutations in the SCO2 gene are the second most common cause of assembly disorders of COX (respiratory chain complex IV). SCO2 protein is a copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II. Mutation in SCO2 gene reduce copper transport or delivery to COX subunits I and II, which results in defective catalytic function of COX (Leary et al., 2004). Interestingly, a relatively high residual COX activity is seen in fibroblasts of the patients (Jaksch et al., 2000).
Metals
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Anirudh J. Chintalapati, Frank A. Barile
Cu has high affinity for metallothionein, a small cysteine-rich protein linked to Cu storage and transport. High Cu levels stimulate metallothionein synthesis. Glutathione, amino acids, ATP, and recently identified copper metallochaperones escort intracellular Cu transport. Physiological Cu-binding ligands are normally present in serum to protect against its toxicity by coordinating the cellular transport of Cu with intracellular enzymes, thereby effectively controlling and balancing its circulating levels. However, the bioavailability of Cu depends on the physiological age of the patient or victim and the amount ingested. Approximately one-half of the Cu consumed by the average adult is absorbed in the GI tract, of which two-thirds is secreted into bile and excreted in feces, with trace amounts eliminated via urine, hair, and sweat.
Copper deficiency, a rare but correctable cause of pancytopenia: a review of literature
Published in Expert Review of Hematology, 2022
Nayha Tahir, Aqsa Ashraf, Syed Hamza Bin Waqar, Abdul Rafae, Leela Kantamneni, Taha Sheikh, Rafiullah Khan
Zinc is an important micronutrient and the second most common trace element after iron, serving as a cofactor in almost hundred biocellular reactions and having roles not limited to protein translation and posttranscriptional modification but also regulating several gene expressions [10,21,22]. Both zinc and copper are absorbed in the duodenum and jejunum via CTR1 and ZIP4, respectively. Copper gets incorporated into metalloprotein metallothionein and metallochaperone ATOX [23,24]. Increased zinc delivery to enterocytes causes upregulation of metallothionein, which is a cysteine-rich metalloprotein regulating copper–zinc homeostasis and binds both trace elements, having more comparative affinity for copper. This leads to high copper-bound metallothionein in the enterocytes, which prevents the escape of copper from the cells, leading to washout of copper from the gastrointestinal tract [10,25,26] (Figure 1).
Global impact of trace non-essential heavy metal contaminants in industrial cannabis bioeconomy
Published in Toxin Reviews, 2022
Louis Bengyella, Mohammed Kuddus, Piyali Mukherjee, Dobgima J. Fonmboh, John E. Kaminski
Cannabis reproductive structures such as seed and flower are arguably highly valued on the market for phytocannabinoids, flavonoids, terpenoids, rich protein sources, and omega-6 and omega-3 oil-rich in a desirable range between 1:2 and 1:3 (Callaway 2004). Understanding the fate of HMs homeostasis in these reproductive structures is thus critical for consumer safety as more than 500 different compounds characterized in Cannabis species are used for several medical interventions (Alves et al. 2020). Plants often counter the destructive effects of HMs by: (i) inactivating the HMs and preventing them from forming a complex with metal chelators such as phytochelatins (PCs) and metallothioneins, and (ii) compartmentation of HMs in idioblasts, vacuoles, and cells walls (Mazen and El Maghraby 1997, Harada et al. 2010). Plants, therefore, rely on low-molecular-weight proteins, the metallochaperones or chelators (such as spermine, spermidine, putrescine, nicotianamine, glutathione, phytochelatins, and other organic acids), metallothioneins, phenylpropanoid compounds (such as flavonoids and anthocyanins), amino acids (proline and histidine), stress-responsive phytohormones and even heat shock proteins (Dalvi and Bhalerao 2013) to effectively counter HMs. Glandular trichomes in cannabis species are microscopic protrusion of variable sizes on flower and leaf surfaces that often-entrap phytocannabinoids (Figure 3) could potentially play a critical role in HMs homeostasis.
Impaired copper transport in schizophrenia results in a copper-deficient brain state: A new side to the dysbindin story
Published in The World Journal of Biological Psychiatry, 2020
Kirsten E. Schoonover, Stacy L. Queern, Suzanne E. Lapi, Rosalinda C. Roberts
Copper plays a key role in development and homeostatic function and is crucial for many cellular functions including monoamine metabolism, mitochondrial activity and myelination (Sato et al. 1994). While copper and its enzymes are found outside of the brain, we will focus on brain. Copper dysfunction results in Wilson’s or Menkes disease, characterised by copper toxicity or deficiency, respectively (Wilson 1934; Menkes et al. 1962). Cellular copper is highly regulated, as free copper can induce oxidative stress and cellular damage (Halliwell and Gutteridge 2007). During normal function, copper is taken from the bloodstream across the blood–brain barrier (BBB) into astrocytes and then neurons via CTR1 at the plasma membrane (Scheiber et al. 2010). Once inside the cell, copper is bound by metallochaperones (Maryon et al. 2013) and delivered to the trans-Golgi network (TGN). ATP7A is located within the TGN (Yamaguchi et al. 1996) and distributes copper to metallochaperones (e.g., SCO1), which transport the copper to their needed location within the cell (e.g., mitochondria) ( Leary et al. 2007; Davies et al. 2013). CTR1 knockdown and/or loss results in developmental defects and lethality (Lee et al. 2001), and total loss of ATP7A results in Menkes disease and lethality (Menkes et al. 1962), exemplifying the incredible importance of these transporters in homeostasis and function.