Instruct: Given a question, retrieve relevant passages that answer the question.
Query: Who first identified metabolism?
One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism.[27] Krebs was a student of extremely important Otto Warburg, and wrote a biography of Warburg by that title in which he presents Warburg as being educated to do for biological chemistry what Fischer did for organic chemistry. Which he did. Krebs discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle.[28][29][30] These discoveries led to Krebs being awarded the Nobel Prize in physiology in 1953,[31] which was shared with the German biochemist Fritz Albert Lipmann who also codiscovered the essential cofactor coenzyme A.
Glycogen storage disease type II, also called Pompe disease, is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme. It is the only glycogen storage disease with a defect in lysosomal metabolism, and the first glycogen storage disease to be identified, in 1932 by the Dutch pathologist J. C. Pompe.
Irisin, a newly identified hormone, was first reported by Bostromet al. in 2012, is a novel myokine which plays an important role in the homeostasis , metabolism and energy balance. Irisin is reported to be involved in insulin resistance in both humans and animal models. Circulating irisin levels progressively decrease with the worsening of the glucose tolerance.
A recent study conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone Irisin and the established adipokine adiponectin with metabolic syndrome, cardio-metabolic variables and cardiovascular disease risk, and they found out that the baseline irisin levels were significantly higher in subjects with metabolic syndrome than in subjects without metabolic syndrome.
There are four possible categories for each marker: poor metabolizer, intermediate metabolizer, extensive metabolizer, or ultra-extensive metabolizer. Different testing companies may call these by different names. Extensive metabolizers (that is, people who are extensive metabolizers of a given type) are the most common, and are the type of people for which drugs are designed. Up to 7% of Caucasians are poor metabolizers of drugs metabolized by the CYP2D6 enzyme.
Genetic polymorphism (mainly CYP2C19*2, CYP2C19*3 and CYP2C19*17) exists for CYP2C19 expression, with approximately 3–5% of European and 15–20% of Asian populations being poor metabolizers with no CYP2C19 function. This may reduce the efficacy of clopidogrel (Plavix). The basis for this reduced effect of clopidogrel in patients who have a gene of reduced activity may seem somewhat paradoxical, but can be understood as follows. Clopidogrel is administered as a “prodrug;” that is, a drug that is inactive when taken, and then depends on the action of an enzyme in the body in order to be activated. In patients who have a gene of reduced activity, clopidogrel may not be metabolized to its active form and therefore not achieve pharmacological effect in the body. In patients with an abnormal CYP2C19 variant certain benzodiazepines should be avoided, such as diazepam (Valium), lorazepam (Ativan), oxazepam (Serax), and temazepam (Restoril). On the basis of their ability to metabolize (S)-mephenytoin or other CYP2C19 substrates, individuals can be classified as extensive metabolizers (EM) or poor metabolizers (PM). Eight variant alleles (CYP2C19*2 to CYP2C19*8) that predict PMs have been identified.
The main direction of scientific activity of D.O. Melnychuk and his scientific school is to study the molecular mechanisms of regulation of metabolism in animals and humans and the search and development of methods of correction of their violations. Together with Acad. M.F. Gulyiv grounded biological role of carboxylation and decarboxylation reactions in the metabolism of macromolecules and of energy in heterotrophic organisms, determined a number of physical and chemical patterns of carbamate formation of proteins and the estimates of their role in the regulation of enzyme activity, discovered the molecular mechanisms of systems metabolic homeostasis in cells in violation of the acid-base balance of the body, identified specific proteins membrane of enterocytes of the small intestine of newborn animals involved in the formation of maternal immunity, analyzed role of phospholipids in the prevention and treatment of gastroenteritis, made a significant contribution to disclosure mechanisms of influence changes in bicarbonate concentration and CO2 in the blood on the intensity of the energy, mineral and nitrogen metabolism, discovered the molecular mechanisms of action hypercapnia and how to transfer the animals to the state of natural and artificial hibernation, also proved prospects of developed technique for veterinary and medical anesthetics, identified the molecular mechanisms of metabolic regulation disorders in diseases of animals and people such as: osteoporosis and osteomalacia, podagra, diabetes, caries, pre- and postnatal and postoperative complications (metabolic acidosis and ketosis), alcohol and ammonium toxicosis, heavy metal toxicosis, feed (food) acidosis in animals and humans, etc. For these research materials published about 700 scientific works, included over 10 monographs and textbooks.
As an alternative explanation, it was suggested that cells could be limited by the rate with which they can dissipate Gibbs energy to the environment. Using combined thermodynamic and stoichiometric metabolic models in flux balance analyses with (i) growth maximization as objective function and (ii) an identified limit in the cellular Gibbs energy dissipation rate, correct predictions of physiological parameters, intracellular metabolic fluxes and metabolite concentrations were achieved.
Metabolic modelling. Essential genes may be also predicted in completely sequenced genomes by metabolic reconstruction, that is, by reconstructing the complete metabolism from the gene content and then identifying those genes and pathways that have been found to be essential in other species. However, this method can be compromised by proteins of unknown function. In addition, many organisms have backup or alternative pathways which have to be taken into account (see figure 1). Metabolic modeling was also used by Basler (2015) to develop a method to predict essential metabolic genes. Flux balance analysis, a method of metabolic modeling, has recently been used to predict essential genes in clear cell renal cell carcinoma metabolism.
In 2009, Larhlimi and Bockmayr presented a new approach called "minimal metabolic behaviors" for the analysis of metabolic networks. Like elementary modes or extreme pathways, these are uniquely determined by the network, and yield a complete description of the flux cone. However, the new description is much more compact. In contrast with elementary modes and extreme pathways, which use an inner description based on generating vectors of the flux cone, MMBs are using an outer description of the flux cone. This approach is based on sets of non-negativity constraints. These can be identified with irreversible reactions, and thus have a direct biochemical interpretation. One can characterize a metabolic network by MMBs and the reversible metabolic space.
Banerjee and his researchers are also interested in the study of metabolic control in cancer pathways. In the past, his lab has identified components of signal transduction pathways that participate in oncogenesis. In addition, they have examined the role of the mitochondrion in controlling cell cycle, particularly that when cells become transformed they choose alternate means of metabolism (a phenomenon referred to as the Warburg effect). Also of interest to Banerjee and his team is studying the effect of signal transduction pathways on the control of cellular metabolism and the proper balance between cellular growth and metabolism that goes awry in cancer.
The urine specimen of newborns should ideally be collected at 48 hours after birth (or within the first 7 days of birth) and after the newborn had at least a first feed to enable early detection and treatment of any identified metabolic disorder. Most babies will test negative for metabolic disorders, however if the newborn’s test shows an abnormal result, Cordlife will immediately contact the attending physician (for example, the Paediatrician), who will then provide instructions on what to do next.
Pharmacometabolomics may be used in a predictive manner to determine the correct course of action in regards to a patient about to undergo some type of drug treatment. This involves determining the metabolic profile of a patient prior to treatment, and correlating metabolic signatures with the outcome of a pharmaceutical treatment course. Analysis of a patient’s metabolic profile can reveal factors that may contribute to altered drug metabolism, allowing for predictions of the overall efficacy of a proposed treatment, as well as potential drug toxicity risks that may differ from the general population. This approach has been used to identify novel or previously characterized metabolic biomarkers in patients, which can be used to predict the expected outcome of that patient following treatment with a pharmaceutical compound. One example of the clinical application of pharmacometabolomics are studies that looked to identify a predictive metabolic marker for the treatment of major depressive disorder (MDD)., In a study with antidepressant Sertraline, the Pharmacometabolomics Network illustrated that metabolic profile at baseline of patients with major depression can inform about treatment outcomes. In addition the study illustrated the power of metabolomics for defining response to placebo and compared response to placebo to response to sertraline and showed that several pathways were common to both. In another study with escitalopram citalopram, metabolomic analysis of plasma from patients with MDD revealed that variations in glycine metabolism were negatively associated with patient outcome upon treatment with selective serotonin reuptake inhibitors (SSRIs), an important drug class involved in the treatment of this disease.
The term "metabolically obese normal weight" (MONW) refers to people with normal weight and body mass index (BMI), who display some metabolic characteristics which increase the risk of developing metabolic syndrome in the same way as obesity. People with MONW have excess visceral fat, and are predisposed to hyperinsulinemia, insulin-resistance and thus predisposition to type 2 diabetes, hypertriglyceridemia, hypertension and premature coronary heart disease orcardiovascular disease.
The BMI does not capture information about percentage body fat (PBF), which is a better predictor of risk due to obesity.
Some studies have suggested that the main factor which explains the metabolic abnormalities in MONW individuals is fat distribution. On the basis of these studies, a scoring method has been proposed to identify MONW individuals, based on the presence of associated diseases or biochemical abnormalities related to insulin resistance.
The metabolism of "C. cupreum" is complex. In an Expressed Sequence Tag (EST) study conducted by Zhang and Yang in 2007 "C. cupreum" demonstrated a diverse expression of genes related to metabolic pathways. In their study the most represented metabolic pathway was glycolysis demonstrating its importance in mycelia cell metabolism. The second most represented category was porphyrin and chlorophyll metabolism, the fungi cannot produce chlorophyll but they have a heme biosynthetic pathway. Genes encoding coproporphyrinogen oxidase, an essential enzyme in the heme biosynthetic pathway were found as well as genes associated with the electron transport chain and oxidative phosphorylation. The citric acid cycle also has a role in its energy metabolism with 18% of metabolic genes relating to TCA cycle function. Saccharide metabolism associated genes were also found for the metabolism of: galactose, fructose, mannose, sucrose, starch, nucleotide sugars, amino sugars, as well as glycoprotein and peptide-protein biosynthesis. Many genes have been identified in this species that support protein biosynthesis and proteolytic systems including: glutamate, methionine and tryptophan metabolism; phenylalanine, valine, leucine and isoleucine degradation; valine, leucine, isoleucine, tyrosine and tryptophan biosynthesis. Proteases produced by "C. cupreum" are involved in pathogen cell wall breakdown and contribute to its biocontrol activity. Biotechnological interest in "C. cupreum" is related to its production of cellulase and laccase. "C. cupreum" is able to degradae catechin.
α-PVT was first identified in Japan in 2013. Its metabolism has been described in literature.
Also, there is evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in PVS with different behavioral features, researchers employed PET, MRI and magnetoencephalographic (MEG) responses to sensory stimulation. In three of the five patients, co-registered PET/MRI correlate areas of relatively preserved brain metabolism with isolated fragments of behavior. Two patients had suffered anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30–40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with higher metabolic rates, that ranged up to 50–80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioral patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioral fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical– pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains (Schiff et al., 2002).
The previous definitions of the metabolic syndrome by the International Diabetes Federation and the revised National Cholesterol Education Program are very similar and they identify individuals with a given set of symptoms as having metabolic syndrome. There are two differences, however: the IDF definition states that if body mass index (BMI) is greater than 30 kg/m, central obesity can be assumed, and waist circumference does not need to be measured. However, this potentially excludes any subject without increased waist circumference if BMI is less than 30. Conversely, the NCEP definition indicates that metabolic syndrome can be diagnosed based on other criteria. Also, the IDF uses geography-specific cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography. These two definitions are much more similar than the original NCEP and WHO definitions.
Cetirizine does not undergo extensive metabolism. It is notably not metabolized by the cytochrome P450 system. Because of this, it does not interact significantly with drugs that inhibit or induce cytochrome P450 enzymes such as theophylline, erythromycin, clarithromycin, cimetidine, or alcohol. While cetirizine does not undergo extensive metabolism or metabolism by the cytochrome P450 enzyme, it does undergo some metabolism by other means, the metabolic pathways of which include oxidation and conjugation. Plasma radioactivity attributed to unchanged cetirizine is more than 90% at 2 hours, 80% at 10 hours, and 70% at 24 hours, indicating limited and slow metabolism. The enzymes responsible for transformation of cetirizine have not been identified.
The clinical value of using "metabolic syndrome" as a diagnosis has previously been debated due to different sets of conflicting and incomplete diagnostic criteria. These concerns have led the American Diabetes Association and the European Association for the Study of Diabetes to issue a joint statement identifying eight major concerns on the clinical utility of the metabolic syndrome diagnosis.
The principal argument has been that when confounding factors such as obesity are accounted for, diagnosis of the metabolic syndrome has a negligible association with the risk of heart disease.
Naturally, since the metabolic syndrome is a disorder of energy distribution and storage, fat accumulation explains for a significant proportion of cardiovascular risk. However, obesity without metabolic syndrome does not confer a significant cardiovascular risk, whereas metabolic syndrome without obesity is associated with a significant risk of diabetes and cardiovascular disease. This association of metabolic syndrome with diabetes can be illustrated by generalized lipodystrophy (near complete absence of adipose tissue). The animals and humans with generalized lipodystrophy develop signs of metabolic syndrome in the absence of adipose tissue; and the metabolic syndrome progresses to type 2 diabetes. Adipose tissue transplantation in transgenic mice with lipodystrophy can cure the type 2 diabetes.
Lee maintained an interest in factors affecting glucose metabolism upon his return to Korea, where he continued his research with published studies of the Korean diet. Building upon work begun in 1928, he investigated the problem of identifying and quantifying the nutritional elements of the staple Korean diet and its effects on metabolism. He identified nutritional sources in these foods for the healthy development of Korean children and adults during the Japanese occupation of Korea.
Metabolic disorders can be present at birth, and many can be identified by routine screening. If a metabolic disorder is not identified early, then it may be diagnosed later in life, when symptoms appear. Specific blood and DNA tests can be done to diagnose genetic metabolic disorders.
Using his systems biology toolbox developed for microorganisms, Jens Nielsen initiated work on human metabolism. In connection with this he developed a comprehensive genome-scale metabolic model for human cells and he was the first to use a human GEM to illustrate the metabolic heterogeneity of cancer metabolism. His work on human metabolism has involved studies of different diseases such as obesity, NAFLD and NASH, and hepatocellular carcinoma. Jens Nielsen further used human GEMs to identify that combined measurements of several glycosaminoglycans can be used as a very strong biomarker for clear cell renal cell carcinoma, probably the first systems biomarker.
The first step in the process is to identify a desired goal to achieve through the improvement or modification of an organism's metabolism. Reference books and online databases are used to research reactions and metabolic pathways that are able to produce this product or result. These databases contain copious genomic and chemical information including pathways for metabolism and other cellular processes. Using this research, an organism is chosen that will be used to create the desired product or result. Considerations that are taken into account when making this decision are how close the organism's metabolic pathway is to the desired pathway, the maintenance costs associated with the organism, and how easy it is to modify the pathway of the organism. "Escherichia coli" ("E. coli") is widely used in metabolic engineering to synthesize a wide variety of products such as amino acids because it is relatively easy to maintain and modify. If the organism does not contain the complete pathway for the desired product or result, then genes that produce the missing enzymes must be incorporated into the organism.
Most of the conditions identified in newborn screening are metabolic disorders that either involve i) lacking an enzyme or the ability to metabolize (or breakdown) a particular component of the diet, like phenylketonuria, ii) abnormality of some component of the blood, especially the hemoglobin protein, or iii) alteration of some component of the endocrine system, especially the thyroid gland. Many of these disorders, once identified, can be treated before more severe symptoms, such as mental retardation or stunted growth, set in.
Metabolism-like reactions could have occurred naturally in early oceans, before the first organisms evolved. Metabolism may predate the origin of life, which may have evolved from the chemical conditions in the earliest oceans. Reconstructions in laboratories show that some of these reactions can produce RNA, and some others resemble two essential reaction cascades of metabolism: glycolysis and the pentose phosphate pathway, that provide essential precursors for nucleic acids, amino acids and lipids. A study at the University of Düsseldorf created phylogenic trees based upon 6 million genes from bacteria and archaea, and identified 355 protein families that were probably present in the LUCA. They were based upon an anaerobic metabolism fixing carbon dioxide and nitrogen. It suggests that the LUCA evolved in an environment rich in hydrogen, carbon dioxide and iron. Following are some observed discoveries and related hypotheses.