Inchemistry,the termsubstrateis highly context-dependent.[1]Broadly speaking, it can refer either to achemical speciesbeing observed in achemical reaction,or to a surface on which other chemical reactions ormicroscopyare performed.
In the former sense, areagentis added to thesubstrateto generate aproductthrough a chemical reaction. The term is used in a similar sense insyntheticandorganic chemistry,where the substrate is the chemical of interest that is being modified. Inbiochemistry,anenzyme substrateis the material upon which anenzymeacts. When referring toLe Chatelier's principle,the substrate is the reagent whose concentration is changed.
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In the latter sense, it may refer to a surface on which other chemical reactions are performed or play a supporting role in a variety of spectroscopic and microscopic techniques, as discussed in the first few subsections below.[2]
Microscopy
editIn three of the most common nano-scalemicroscopytechniques,atomic force microscopy(AFM),scanning tunneling microscopy(STM), andtransmission electron microscopy(TEM), a substrate is required for sample mounting. Substrates are often thin and relatively free of chemical features or defects.[3]Typically silver, gold, or silicon wafers are used due to their ease of manufacturing and lack of interference in the microscopy data. Samples are deposited onto the substrate in fine layers where it can act as a solid support of reliable thickness and malleability.[2][4]Smoothness of the substrate is especially important for these types of microscopy because they are sensitive to very small changes in sample height.[citation needed]
Various other substrates are used in specific cases to accommodate a wide variety of samples. Thermally-insulating substrates are required for AFM of graphite flakes for instance,[5]and conductive substrates are required for TEM. In some contexts, the word substrate can be used to refer to the sample itself, rather than the solid support on which it is placed.
Spectroscopy
editVariousspectroscopictechniques also require samples to be mounted on substrates, such aspowder diffraction.This type of diffraction, which involves directing high-powered X-rays at powder samples to deduce crystal structures, is often performed with anamorphoussubstrate such that it does not interfere with the resulting data collection. Silicon substrates are also commonly used because of their cost-effective nature and relatively little data interference in X-ray collection.[6]
Single-crystalsubstrates are useful inpowder diffractionbecause they are distinguishable from the sample of interest in diffraction patterns by differentiating by phase.[7]
Atomic layer deposition
editInatomic layer deposition,the substrate acts as an initial surface on which reagents can combine to precisely build up chemical structures.[8][9]A wide variety of substrates are used depending on the reaction of interest, but they frequently bind the reagents with some affinity to allow sticking to the substrate.[citation needed]
The substrate is exposed to different reagents sequentially and washed in between to remove excess. A substrate is critical in this technique because the first layer needs a place to bind to such that it is not lost when exposed to the second or third set of reagents.[citation needed][10]
Biochemistry
editInbiochemistry,the substrate is amoleculeupon which anenzymeacts. Enzymescatalyzechemical reactionsinvolving the substrate(s). In the case of a single substrate, the substrate bonds with the enzymeactive site,and anenzyme-substrate complexis formed. The substrate is transformed into one or moreproducts,which are then released from the active site. The active site is then free to accept another substrate molecule. In the case of more than one substrate, these may bind in a particular order to the active site, before reacting together to produce products. A substrate is called 'chromogenic' if it gives rise to a coloured product when acted on by an enzyme. In histological enzyme localization studies, the colored product of enzyme action can be viewed under a microscope, in thin sections of biological tissues. Similarly, a substrate is called 'fluorogenic' if it gives rise to a fluorescent product when acted on by an enzyme.[citation needed]
For example, curd formation (rennetcoagulation) is a reaction that occurs upon adding the enzymerenninto milk. In this reaction, the substrate is a milk protein (e.g.,casein) and the enzyme is rennin. The products are two polypeptides that have been formed by the cleavage of the larger peptide substrate. Another example is thechemical decompositionofhydrogen peroxidecarried out by the enzymecatalase.As enzymes arecatalysts,they are not changed by the reactions they carry out. The substrate(s), however, is/are converted to product(s). Here, hydrogen peroxide is converted to water and oxygen gas.
- E + S ⇌ ES → EP ⇌ E + P
- Where E is enzyme, S is substrate, and P is product
While the first (binding) and third (unbinding) steps are, in general,reversible,the middle step may beirreversible(as in the rennin and catalase reactions just mentioned) or reversible (e.g. many reactions in theglycolysismetabolic pathway).
By increasing the substrate concentration, the rate of reaction will increase due to the likelihood that the number of enzyme-substrate complexes will increase; this occurs until theenzymeconcentration becomes thelimiting factor.
Substrate promiscuity
editAlthough enzymes are typically highly specific, some are able to perform catalysis on more than one substrate, a property termedenzyme promiscuity.An enzyme may have many native substrates and broadspecificity(e.g. oxidation bycytochrome p450s) or it may have a single native substrate with a set of similar non-native substrates that it can catalyse at some lower rate. The substrates that a given enzyme may react within vitro,in a laboratory setting, may not necessarily reflect the physiological, endogenous substrates of the enzyme's reactionsin vivo.That is to say that enzymes do not necessarily perform all the reactions in the body that may be possible in the laboratory. For example, whilefatty acid amide hydrolase(FAAH) can hydrolyze the endocannabinoids2-arachidonoylglycerol(2-AG) andanandamideat comparable ratesin vitro,genetic or pharmacological disruption of FAAH elevates anandamide but not 2-AG, suggesting that 2-AG is not an endogenous,in vivosubstrate for FAAH.[11]In another example, theN-acyl taurines (NATs) are observed to increase dramatically in FAAH-disrupted animals, but are actually poorin vitroFAAH substrates.[12]
Sensitivity
editSensitive substrates,also known assensitive index substrates,are drugs that demonstrate an increase inAUCof ≥5-fold withstrong index inhibitorsof a givenmetabolic pathwayin clinicaldrug-drug interaction(DDI) studies.[13]
Moderate sensitive substratesare drugs that demonstrate an increase in AUC of ≥2 to <5-fold with strong index inhibitors of a given metabolic pathway in clinical DDI studies.[13]
Interaction between substrates
editMetabolism by the samecytochrome P450isozyme can result in several clinically significant drug-drug interactions.[14]
See also
editReferences
edit- ^IUPAC,Compendium of Chemical Terminology,2nd ed. (the "Gold Book" ) (1997). Online corrected version: (2006–) "substrate".doi:10.1351/goldbook.S06082
- ^ab"Substrates for AFM, STM".emsdiasum.Retrieved2019-12-01.
- ^Hornyak, G. L.; Peschel, St.; Sawitowski, Th.; Schmid, G. (1998-04-01). "TEM, STM and AFM as tools to study clusters and colloids".Micron.29(2): 183–190.doi:10.1016/S0968-4328(97)00058-9.ISSN0968-4328.
- ^"Silicon Wafers for AFM, STM".Electron Microscopy Sciences.Retrieved2019-12-01.
- ^Zhang, Hang; Huang, Junxiang; Wang, Yongwei; Liu, Rui; Huai, Xiulan; Jiang, Jingjing; Anfuso, Chantelle (2018-01-01). "Atomic force microscopy for two-dimensional materials: A tutorial review".Optics Communications.Optoelectronics and Photonics Based on Two-dimensional Materials.406:3–17.doi:10.1016/j.optcom.2017.05.015.ISSN0030-4018.
- ^"Specimen Holders - X-ray Diffraction".Bruker.Retrieved2019-12-01.
- ^Clark, Christine M.;Dutrow, Barbara L."Single-crystal X-ray Diffraction".Geochemical Instrumentation and Analysis.
- ^Detavernier, Christophe; Dendooven, Jolien; Sree, Sreeprasanth Pulinthanathu; Ludwig, Karl F.; Martens, Johan A. (2011-10-17). "Tailoring nanoporous materials by atomic layer deposition".Chemical Society Reviews.40(11): 5242–5253.doi:10.1039/C1CS15091J.ISSN1460-4744.PMID21695333.
- ^Xie, Qi; Deng, Shaoren; Schaekers, Marc; Lin, Dennis; Caymax, Matty; Delabie, Annelies; Qu, Xin-Ping; Jiang, Yu-Long; Deduytsche, Davy; Detavernier, Christophe (2012-06-22). "Germanium surface passivation and atomic layer deposition of high-kdielectrics—a tutorial review on Ge-based MOS capacitors".Semiconductor Science and Technology.27(7): 074012.doi:10.1088/0268-1242/27/7/074012.ISSN0268-1242.
- ^Sennepin, Alexis D.; Charpentier, Stéphane; Normand, Thierry; Sarré, Cédric; Legrand, Alain; Mollet, Lucile M. (2009-10-01)."Multiple reprobing of Western blots after inactivation of peroxidase activity by its substrate, hydrogen peroxide".Analytical Biochemistry.393(1): 129–131.doi:10.1016/j.ab.2009.06.004.ISSN0003-2697.
- ^Cravatt, B. F.; Demarest, K.; Patricelli, M. P.; Bracey, M. H.; Gaing, D. K.; Martin, B. R.; Lichtman, A. H. (2001)."Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase".Proc. Natl. Acad. Sci. USA.98(16): 9371–9376.Bibcode:2001PNAS...98.9371C.doi:10.1073/pnas.161191698.PMC55427.PMID11470906.
- ^Saghatelian, A.; Trauger, S. A.; Want, E. J.; Hawkins, E. G.;Siuzdak, G.;Cravatt, B.F. (2004). "Assignment of Endogenous Substrates to Enzymes by Global Metabolite Profiling".Biochemistry.43(45): 14322–14339.CiteSeerX10.1.1.334.206.doi:10.1021/bi0480335.PMID15533037.
- ^ab"Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers".U.S. Food and Drug Administration. 26 May 2021.
- ^Ogu, CC; Maxa, JL (2000)."Drug interactions due to cytochrome P450".Proceedings (Baylor University. Medical Center).13(4): 421–423.doi:10.1080/08998280.2000.11927719.PMC1312247.PMID16389357.