R

two major types of regulatory enzymes:

(1)covalently modulated enzymes, and

(2)allosteric enzymes.

Covalently modulated enzymes can be interconverted between active and inactive (or less active) forms by the covalent attachment (or removal) of a modulating metabolite by other enzymes. Hence the activity of one enzyme can, under certain conditions, be regulated by other enzymes. Glycogen phosphorylase, an oligomeric protein with four major subunits (tetramer), is a classic example of a covalently modulated enzyme. The enzyme occurs in two forms: (1) phosphorylase a, the more active form, and (2) phosphorylase b, the less active form. In order for the enzyme to possess maximal catalytic activity (i.e., be phosphorylase a) certain serine residue on all four subunits must have a phosphate covalently attached. If, due to other regulatory signals it has received, the enzyme phosphorylase phosphatase hydrolytically cleaves and removes the phosphate group from the four subunits, the tetramer dissociates into the inactive (or much less active) dimer, phosphorylase b. Another enzyme, phosphorylase kinase, is able to rephosphorylate the four specific serine residues of the four subunits at the expense of ATP and regenerate the active phosphorylase a tetramer.

Allosteric enzymes are enzymes that possess a special site on their surfaces that is distinct from the enzyme’s catalytic site and to which specific metabolites (called effectors or modulators) are reversibly and noncovalently bound. The allosteric binding site is as specific for a particular metabolite as is the catalytic site, but it cannot catalyze a reaction, only bind the effector. The binding of the effector causes a conformation change in the enzyme such that its catalytic activity is impaired or stopped. Allosteric enzymes are normally the first enzymes in, or are near the beginning of, a multienzyme system. The very last product produced by the multienzyme system (the end product) may act as a specific inhibitor of the allosteric enzyme by binding to that enzyme’s allosteric site. The binding consequently causes a conformation

change to occur in the enzyme, which inactivates it. A classic example of an allosteric enzyme in a multienzyme sequence is the enzyme L-threonine dehydratase, which is the initial enzyme in the enzyme sequence that catalyzes the conversion of L-threonine to L-isoleucine. This reaction occurs in five enzyme-catalyzed steps. The end product, L-isoleucine, strongly inhibits L-threonine dehydratase, the first enzyme in the fiveenzyme sequence. No other intermediate in the sequence is able to inhibit the enzyme. This kind of repression is called feedback or end-product inhibition.

It should be noted that allosteric control may be negative (as in the example above) or positive. In positive control the effector binds to an allosteric site and stimulates the activity of the enzyme. Furthermore, some allosteric enzymes respond to two or more specific modulators with each modulator having its own specific binding site on the enzyme. An allosteric enzyme that has only one specific modulator is called monovalent, whereas an enzyme responding to two or more specific modulators is called polyvalent. Combinations of the above possibilities could lead to very fine tuning of the enzymes involved in the synthesis and/or degradation of metabolites.

Note that in the two examples above, the common denominator is the structural change that occurs upon execution of the

mechanism. See also METABOLITE, REPRESSIBLE ENZYME.

Regulatory Genes Genes whose primary function is to control the state of synthesis of the products of other genes.

Regulatory Sequence A D NA s e q u e n c e involved in regulating the expression of a gene, e.g., a promoter or operator region (in the DNA molecule). See also OPERATOR,

PROMOTER, DOWN PROMOTER MUTATIONS, DOWN

REGULATING, TRANSCRIPTION FACTORS.

Remediation The cleanup or containment (if chemicals are moving) of a hazardous waste disposal site to the satisfaction of the applicable regulatory agency [e.g., the Environmental Protection Agency (EPA)]. Such cleanup can sometimes be accomplished via

use of microorganisms that have been adapted (naturally or via genetic engineering) to consume those chemical wastes present in the disposal site. See also ACCLIMATIZATION.

Renaturation The return to the natural structure of a protein or nucleic acid from a denatured (more random coil) state. For example, a protein may be denatured [lose its native (natural) structure] by exposure to surfactants such as SDS or to changes in the pH of the medium. If the surfactant is slowly removed, or the pH is slowly readjusted to the optimum for the protein, it will refold (snap) back into its original (native) form. See also NATIVE

CONFIGURATION, DENATURATION, SDS.

Renin A proteolytic enzyme secreted by the juxtaglomerular cells of the kidney. Its release is stimulated by decreased arterial pressure and renal blood flow resulting from decreased extracellular fluid volume. It catalyzes the formation of angiotensin I from hypertensinogen. Angiotensin I is converted to angiotensin II by another enzyme located in the endothelial cells of the lungs. Angiotensin II then causes the increase in the force of the heartbeat and constricts the arterioles. This scenario causes a rise in the blood pressure and is thus a cause of hypertension (high blood pressure). See also HOMEOSTASIS,

RENIN INHIBITORS, ATRIAL PEPTIDES.

Renin Inhibitors Those chemicals that act to block the hypertensive (i.e., high blood pres- sure-inducing) effect of the enzyme, renin.

See also HOMEOSTASIS, RENIN INHIBITORS,

ATRIAL PEPTIDES.

Rennin See CHYMOSIN.

Reovirus A virus containing double-stranded RNA. It is isolated from the respiratory and intestinal tracts of humans and other mammals. The prefix “reo-” is an acronym for respiratory enteric orphan. See also RETROVIRUSES.

Reperfusion The restoration of blood flow to an occluded (blocked) blood vessel. May be done biochemically (e.g., via tissue plasminogen activator) or via surgery. See also HUMAN

SUPEROXIDE DISMUTASE (hSOD), LAZAROIDS.

Replication (of DNA) Reproduction of a DNA molecule (inside a cell). This process can be viewed as occurring in stages, in which the first stage consists of an enzyme

“unwinding” the double helix of the DNA molecule at a replication origin, forming a replication fork. At the replication fork, the two separated (DNA) strands serve as templates for new DNA synthesis. That new DNA synthesis is accomplished on each strand via enzymes known as DNA polymerase, which travel along each (single) strand making a second complementary strand by catalyzing the addition of DNA bases (to the new, growing strands). The end result is two new double helices (DNA molecules), each of which has one chain from the original DNA molecule and one chain that was newly synthesized by the DNA polymerase enzymes. See also DEOXYRIBO-

N U C L E I C A C I D (D N A ), D N A P O L Y M E R A S E ,

ENZYME, REPLICATION FORK, DUPLEX, DOUBLE

HELIX, BASE PAIR (bp).

or growth factor, the researchers need to quickly know when one of the candidate drugs has had the desired effect on the cell of interest. By prior insertion into that cell of a gene (e.g., which causes bioluminescence or a certain chemical to be produced by the cell when signal transduction has taken place), that cell “reports” (when a candidate drug has had the desired effect on the cell) by producing the bioluminescence or chemical (coded for by the reporter gene) which can be rapidly detected by the researcher (e.g., via light sensors or biosensors placed adjacent to the cell). See also GENE, GENETIC

ENGINEERING, GENETIC CODE, CODING SEQUENCE,

CELL, BIOLUMINESCENCE, CELL CULTURE, SIGNAL

TRANSDUCTION, HORMONE, GROWTH FACTOR,

BIOSENSORS (ELECTRONIC).

Repressible Enzyme An enzyme whose synthesis (rate of production) is inhibited (repressed) when the product that it (or the enzyme within a multienzyme sequence) synthesizes is present in high concentrations. It is a way of shutting down the synthesis of an enzyme whose product is not required because so much of it is readily available to the cell. When that enzyme product is no longer available (e.g., because the cell has consumed that product), more of the enzyme is synthesized (to catalyze production of more product). See also REPRESSION (OF AN

ENZYME), REGULATORY ENZYME, ENZYME.

Repression (of an enzyme) The prevention

Rof synthesis of certain enzymes when their reaction products are present. See also

REPRESSIBLE ENZYME.

Repression (of gene transcription/translation) The inhibition of transcription (or translation) by the binding of a repressor protein to a specific site on the DNA (or RNA) molecule. The repressor molecule is the product of a repressor gene. See also

REPRESSOR (PROTEIN), TRANSCRIPTION, TRANSLA-

TION, DEOXYRIBONUCLEIC ACID (DNA).

Repressor (protein) The product of a regulatory gene, it is a protein that combines both with an inducer (or corepressor) and with an operator region (e.g., of DNA). See also

INDUCERS, COREPRESSOR, OPERATOR, REPRESSION

(OF GENE TRANSCRIPTION/TRANSLATION).

Research Foundation for Microbiological Diseases (includes Institute of Physical and Chemical Research) Also known as Riken. A Japanese institution that performs research on infectious diseases, among other research. See also

ALLERGY AND INFECTIOUS DISEASES (NIAID),

KOSEISHO.

Residue (of chemical within a foodstuff)

See MAXIMUM RESIDUE LEVEL (MRL).

Residue (portion of a protein molecule)

See MINIMIZED PROTEINS.

Respiration Oxidative process in living cells in which oxygen or an inorganic compound serves as the terminal (final, ultimate) electron acceptor. Aerobic organisms obtain most of their energy from the oxidation of organic fuels. This process is known as res-

piration. See also OXIDATION-REDUCTION REACTION, REDUCTION

OXIDATION, OXIDIZING AGENT.

Restriction Endoglycosidases A class of enzymes, each of which cleaves (cuts) oligosaccharides (e.g., the side chains on glycoprotein molecules) at a specific location within the chain. They are important tools in carbohydrate engineering, enabling the carbohydrate engineer to sequence (i.e., determine the structure of) existing oligosaccharides, to create different oligosaccharides, and to create different glycoproteins via removal/addition/change of the oligosaccharide chains on glycoprotein molecules.

See also OLIGOSACCHARIDES, GLYCOPROTEIN,

CARBOHYDRATE ENGINEERING, GLYCOSIDASES,

ENDOGLYCOSIDASE, EXOGLYCOSIDASE, GLYCO-

FORM, GLYCOBIOLOGY, GLYCOSYLATION.

Restriction Endonucleases A class of enzymes that cleave (cut) DNA at a specific and unique internal location along its length. These enzymes are naturally produced by bacteria that use them as a defense mechanism against viral infection. The enzymes chop up the viral nucleic acids and hence their function is destroyed. Discovered in the late 1970s by Werner Arber, Hamilton Smith, and Daniel Nathans, restriction endonucleases are important tools in genetic engineering, enabling the biotechnologist to splice new genes into the location(s) of a molecule of DNA where a restriction endonuclease has created a gap

(via cleavage of the DNA). See also VECTOR,

ENZYME, POLYMERASE, GENE, GENETIC ENGINEER-

ING, GENE SPLICING, ELECTROPHORESIS.

Restriction Enzymes See RESTRICTION ENDONU-

CLEASES.

Restriction Fragment Length Polymorphism (RFLP) Technique A “genetic mapping” technique that analyzes the specific sequence of bases (i.e., nucleotides) in a piece of DNA (from an organism). Since the specific sequence of bases in DNA molecules is different for each species, strain, variety, and individual (due to DNA polymorphism), RFLP can be utilized to “map” those DNA molecules (for plant breeding purposes, for criminal investigation purposes, etc.). See also GENETIC MAP, SEQUENCE

(OF A DNA MOLECULE), RANDOM AMPLIFIED

POLYMORPHIC DNA (RAPD) TECHNIQUE, DEOXY-

RIBONUCLEIC ACID (DNA), GENOME, PHYSICAL

MAP (OF GENOME), LINKAGE, LINKAGE GROUP,

MARKER (GENETIC MARKER), LINKAGE MAP,

TRAIT, BASE PAIR (bp), DNA PROFILING, POLYMOR-

PHISM (CHEMICAL), NUCLEIC ACIDS, GENETIC

CODE, INFORMATIONAL MOLECULES.

Restriction Map A pictorial representation of the specific restriction sites (i.e., nucleotide sequences that are cleaved by given restriction endonucleases) in a DNA molecule (e.g., plasmid or chromosome). See also

RESTRICTION SITE, RESTRICTION ENDONUCLEASES,

DNA.

Restriction Site A nucleotide sequence (of base pairs) in a DNA molecule that is “recognized,” and cleaved by a given restriction endonuclease. See also N U C L E O T I D E ,

SEQUENCE (OF A DNA MOLECULE), BASE PAIR (bp),

DNA, RESTRICTION ENDONUCLEASES, RESTRICTION

MAP.

Resveratrol Also known as 3,5,4 trihydroxy stilbene, it is a naturally occurring (in grapes) anti-fungal agent (e.g., against grape fungus). Resveratrol is thought to be responsible for the fact that consumption of red wine by humans helps those humans’ blood fat (triglycerides) levels and blood cholesterol levels to be lowered; thereby reducing risk of cardiovascular disease. Resveratrol is a phytochemical produced by certain plants in response to “wounding” (e.g., by fungal growth on plant) or other stress. Plants that

produce resveratrol include red grapes, mulberries, soybeans, and peanuts. Resveratrol inhibits cell mutations, stimulates at least one enzyme that can inactivate certain carcinogens, and (when consumed by humans) lowers blood cholesterol and blood fat lev-

els. See also PHYTOCHEMICALS, SOYBEAN PLANT, FUNGUS, CARCINOGEN, CELL, MUTATION,

TRIGLYCERIDES, CHOLESTEROL, ENZYME, ATH-

EROSCLEROSIS, CORONARY HEART DISEASE (CHD).