A carotenoid constituent of visual pigments. It is the oxidized form of retinol which functions as the active component of the visual cycle. It is bound to the protein opsin forming the complex rhodopsin. When stimulated by visible light, the retinal component of the rhodopsin complex undergoes isomerization at the 11-position of the double bond to the cis-form; this is reversed in "dark" reactions to return to the native trans-configuration.
A metalloflavoprotein enzyme involved the metabolism of VITAMIN A, this enzyme catalyzes the oxidation of RETINAL to RETINOIC ACID, using both NAD+ and FAD coenzymes. It also acts on both the 11-trans- and 13-cis-forms of RETINAL.
Oxidoreductases that are specific for ALDEHYDES.
An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).
A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization.
A subclass of retinol-binding proteins that take part in the intracellular storage and transport of RETINOL. They are both functionally and structurally distinct from PLASMA RETINOL-BINDING PROTEINS.
Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of CAROTENOIDS found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products.
An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. This enzyme was formerly classified as EC 1.1.1.70.
A subclass of enzymes which includes all dehydrogenases acting on primary and secondary alcohols as well as hemiacetals. They are further classified according to the acceptor which can be NAD+ or NADP+ (subclass 1.1.1), cytochrome (1.1.2), oxygen (1.1.3), quinone (1.1.5), or another acceptor (1.1.99).
Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a non-covalently-bound ligand.
Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.
A nutritional condition produced by a deficiency of VITAMIN A in the diet, characterized by NIGHT BLINDNESS and other ocular manifestations such as dryness of the conjunctiva and later of the cornea (XEROPHTHALMIA). Vitamin A deficiency is a very common problem worldwide, particularly in developing countries as a consequence of famine or shortages of vitamin A-rich foods. In the United States it is found among the urban poor, the elderly, alcoholics, and patients with malabsorption. (From Cecil Textbook of Medicine, 19th ed, p1179)
A zinc-containing enzyme which oxidizes primary and secondary alcohols or hemiacetals in the presence of NAD. In alcoholic fermentation, it catalyzes the final step of reducing an aldehyde to an alcohol in the presence of NADH and hydrogen.
The posterior of the three primitive cerebral vesicles of an embryonic brain. It consists of myelencephalon, metencephalon, and isthmus rhombencephali from which develop the major BRAIN STEM components, such as MEDULLA OBLONGATA from the myelencephalon, CEREBELLUM and PONS from the metencephalon, with the expanded cavity forming the FOURTH VENTRICLE.
The layer of pigment-containing epithelial cells in the RETINA; the CILIARY BODY; and the IRIS in the eye.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
The processes occurring in early development that direct morphogenesis. They specify the body plan ensuring that cells will proceed to differentiate, grow, and diversify in size and shape at the correct relative positions. Included are axial patterning, segmentation, compartment specification, limb position, organ boundary patterning, blood vessel patterning, etc.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The rate dynamics in chemical or physical systems.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

Structure and function in rhodopsin: kinetic studies of retinal binding to purified opsin mutants in defined phospholipid-detergent mixtures serve as probes of the retinal binding pocket. (1/702)

In the current standard procedure for preparation of mammalian rhodopsin mutants, transfected COS-1 cells expressing the mutant opsin genes are treated with 5 microM 11-cis-retinal before detergent solubilization for purification. We found that binding of 11-cis-retinal to opsin mutants with single amino acid changes at Trp-265 (W265F,Y,A) and a retinitis pigmentosa mutant (A164V) was far from complete and required much higher concentrations of 11-cis-retinal. By isolation of the expressed opsins in a stable form, kinetic studies of retinal binding to the opsins in vitro have been carried out by using defined phospholipid-detergent mixtures. The results show wide variation in the rates of 11-cis-retinal binding. Thus, the in vitro reconstitution procedure serves as a probe of the retinal-binding pocket in the opsins. Further, a method is described for purification and characterization of the rhodopsin mutants after retinal binding to the opsins in vitro.  (+info)

Metabolism of retinaldehyde isomers in pregnant rats: 13-cis- and all-trans-retinaldehyde, but not 9-cis-retinaldehyde, yield very similar patterns of retinoid metabolites. (2/702)

Retinaldehyde (RAL), a key intermediate in retinoid metabolism, acts as a retinoic acid (RA) precursor, but is also reduced to retinol (ROH), which can subsequently be esterified to retinyl esters, the storage form of vitamin A. Limited information is available on the metabolism of geometric isomers of RAL as well as on the transplacental distribution of their metabolites, including RA isomers. Such information would be very helpful for the assessment of the teratogenic potency of RAL isomers, as teratogenesis represents a major side effect of retinoid use in pharmacotherapy. In the present study we examined concentrations of retinoids in plasma, maternal tissues, and embryos of pregnant rats 2 h after a single oral dose (100 mg/kg body weight) of all-trans-, 13-cis-, or 9-cis-RAL on gestational day 13. The main findings of this study were the very similar patterns of retinoid metabolites (consisting of retinoids with mainly the all-trans-configuration) after administration of all-trans- and 13-cis-RAL, and the high concentrations of 9-cis-RA, 9,13-dicis-RA, and 9-cis-retinoyl-beta-D-glucuronide after dosing with 9-cis-RAL. In addition, all-trans-RA as a RAL metabolite reached the embryos to a much greater extent than any of its cis-isomers. The results are discussed in view of in vitro data on enzymes involved in the biotransformation of RAL isomers.  (+info)

Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease. (3/702)

Many substrates for P-glycoprotein, an ABC transporter that mediates multidrug resistance in mammalian cells, have been shown to stimulate its ATPase activity in vitro. In the present study, we used this property as a criterion to search for natural and artificial substrates and/or allosteric regulators of ABCR, the rod photoreceptor-specific ABC transporter responsible for Stargardt disease, an early onset macular degeneration. ABCR was immunoaffinity purified to apparent homogeneity from bovine rod outer segments and reconstituted into liposomes. All-trans-retinal, a candidate ligand, stimulates the ATPase activity of ABCR 3-4-fold, with a half-maximal effect at 10-15 microM. 11-cis- and 13-cis-retinal show similar activity. All-trans-retinal stimulates the ATPase activity of ABCR with Michaelis-Menten behavior indicative of simple noncooperative binding that is associated with a rate-limiting enzyme-substrate intermediate in the pathway of ATP hydrolysis. Among 37 structurally diverse non-retinoid compounds, including nine previously characterized substrates or sensitizers of P-glycoprotein, only four show significant ATPase stimulation when tested at 20 microM. The dose-response curves of these four compounds are indicative of multiple binding sites and/or modes of interaction with ABCR. Two of these compounds, amiodarone and digitonin, can act synergistically with all-trans-retinal, implying that they interact with a site or sites on ABCR different from the one with which all-trans-retinal interacts. Unlike retinal, amiodarone appears to interact with both free and ATP-bound ABCR. Together with clinical observations on Stargardt disease and the localization of ABCR to rod outer segment disc membranes, these data suggest that retinoids, and most likely retinal, are the natural substrates for transport by ABCR in rod outer segments. These observations have significant implications for understanding the visual cycle and the pathogenesis of Stargardt disease and for the identification of compounds that could modify the natural history of Stargardt disease or other retinopathies associated with impaired ABCR function.  (+info)

Xenopus cytosolic thyroid hormone-binding protein (xCTBP) is aldehyde dehydrogenase catalyzing the formation of retinoic acid. (4/702)

Amino acid sequencing of an internal peptide fragment derived from purified Xenopus cytosolic thyroid hormone-binding protein (xCTBP) demonstrates high similarity to the corresponding sequence of mammalian aldehyde dehydrogenase 1 (ALDH1) (Yamauchi, K., and Tata, J. R. (1994) Eur. J. Biochem. 225, 1105-1112). Here we show that xCTBP was co-purified with ALDH and 3,3',5-triiodo-L-thyronine (T3) binding activities. By photoaffinity labeling with [125I]T3, a T3-binding site in the xCTBP was estimated to reside in amino acid residues 93-114, which is distinct from the active site of the enzyme but present in the NAD+ binding domain. The amino acid sequences deduced from the two isolated xALDH1 cDNAs (xALDH1-I and xALDH1-II) were 94.6% identical to each other and very similar to those of mammalian ALDH1 enzymes. The two recombinant xALDH1 proteins exhibit both T3 binding activity and ALDH activity converting retinal to retinoic acid (RA), which are similar to those of xCTBP. The mRNAs were present abundantly in kidney and intestine of adult female Xenopus. Interestingly, their T3 binding activities were inhibited by NAD+ and NADH but not by NADP+ and NADPH, whereas NAD+ was required for their ALDH activities. Our results demonstrate that xCTBP is identical to ALDH1 and suggest that this protein might modulate RA synthesis and intracellular level of free T3.  (+info)

Differential mechanisms of retinoid transfer from cellular retinol binding proteins types I and II to phospholipid membranes. (5/702)

Cellular retinol-binding proteins types I and II (CRBP-I and CRBP-II) are known to differentially facilitate retinoid metabolism by several membrane-associated enzymes. The mechanism of ligand transfer to phospholipid small unilamellar vesicles was compared in order to determine whether differences in ligand trafficking properties could underlie these functional differences. Unidirectional transfer of retinol from the CRBPs to membranes was monitored by following the increase in intrinsic protein fluorescence that occurs upon ligand dissociation. The results showed that ligand transfer of retinol from CRBP-I was >5-fold faster than transfer from CRBP-II. For both proteins, transfer of the other naturally occurring retinoid, retinaldehyde, was 4-5-fold faster than transfer of retinol. Rates of ligand transfer from CRBP-I to small unilamellar vesicles increased with increasing concentration of acceptor membrane and with the incorporation of the anionic lipids cardiolipin or phosphatidylserine into membranes. In contrast, transfer from CRBP-II was unaffected by either membrane concentration or composition. Preincubation of anionic vesicles with CRBP-I was able to prevent cytochrome c, a peripheral membrane protein, from binding, whereas CRBP-II was ineffective. In addition, monolayer exclusion experiments demonstrated differences in the rate and magnitude of the CRBP interactions with phospholipid membranes. These results suggest that the mechanisms of ligand transfer from CRBP-I and CRBP-II to membranes are markedly different as follows: transfer from CRBP-I may involve and require effective collisional interactions with membranes, whereas a diffusional process primarily mediates transfer from CRBP-II. These differences may help account for their distinct functional roles in the modulation of intracellular retinoid metabolism.  (+info)

Simulation analysis of the retinal conformational equilibrium in dark-adapted bacteriorhodopsin. (6/702)

In dark-adapted bacteriorhodopsin (bR) the retinal moiety populates two conformers: all-trans and (13,15)cis. Here we examine factors influencing the thermodynamic equilibrium and conformational transition between the two forms, using molecular mechanics and dynamics calculations. Adiabatic potential energy mapping indicates that whereas the twofold intrinsic torsional potentials of the C13==C14 and C15==N16 double bonds favor a sequential torsional pathway, the protein environment favors a concerted, bicycle-pedal mechanism. Which of these two pathways will actually occur in bR depends on the as yet unknown relative weight of the intrinsic and environmental effects. The free energy difference between the conformers was computed for wild-type and modified bR, using molecular dynamics simulation. In the wild-type protein the free energy of the (13,15)cis retinal form is calculated to be 1.1 kcal/mol lower than the all-trans retinal form, a value within approximately kBT of experiment. In contrast, in isolated retinal the free energy of the all-trans state is calculated to be 2.1 kcal/mol lower than (13,15)cis. The free energy differences are similar to the adiabatic potential energy differences in the various systems examined, consistent with an essentially enthalpic origin. The stabilization of the (13,15)cis form in bR relative to the isolated retinal molecule is found to originate from improved protein-protein interactions. Removing internal water molecules near the Schiff base strongly stabilizes the (13,15)cis form, whereas a double mutation that removes negative charges in the retinal pocket (Asp85 to Ala; Asp212 to Ala) has the opposite effect.  (+info)

Bothnia dystrophy caused by mutations in the cellular retinaldehyde-binding protein gene (RLBP1) on chromosome 15q26. (7/702)

PURPOSE: To determine the chromosomal location and to identify the gene causing a type of retinitis punctata albescens, called Bothnia dystrophy, found in a restricted geographic area in northern Sweden. METHODS: Twenty patients from seven families originating from a restricted geographic area in northern Sweden were clinically examined. Microsatellite markers were analyzed in all affected and unaffected family members. Direct genomic sequencing of the gene encoding cellular retinaldehyde-binding protein was performed after the linkage analysis had been completed. RESULTS: Affected individuals showed night blindness from early childhood with features consistent with retinitis punctata albescens and macular degeneration. The responsible gene was mapped to 15q26, the same region to which the cellular retinaldehyde-binding protein gene has been assigned. Subsequent analysis showed all affected patients were homozygous for a C to T substitution in exon 7 of the same gene, leading to the missense mutation Arg234Trp. Analysis of marker haplotypes suggested that all cases had a common ancestor who carried the mutation. CONCLUSIONS: A missense mutation in the cellular retinaldehyde-binding protein gene is the cause of Bothnia dystrophy. The disease is a local variant of retinitis punctata albescens that is common in northern Sweden due to a founder mutation.  (+info)

Recessive mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein in a form of retinitis punctata albescens. (8/702)

PURPOSE: To determine the frequency and spectrum of mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein (CRALBP) in patients with hereditary retinal degeneration. METHODS: The single-strand conformation polymorphism (SSCP) technique and a direct genomic sequencing technique were used to screen the coding exons of this gene (exons 2-8) for mutations in 324 unrelated patients with recessive or isolate retinitis pigmentosa, retinitis punctata albescens, Leber congenital amaurosis, or a related disease. Variant DNA fragments revealed by SSCP analysis were subsequently sequenced. Selected alleles that altered the coding region or intron splice sites were evaluated further through segregation analysis in the families of the index cases. RESULTS: Four novel mutations were identified in this gene among three unrelated patients with recessively inherited retinitis punctata albescens. Two of the mutations were missense: one was a frameshift, and one affected a canonical splice donor site. CONCLUSIONS: Recessive mutations in the RLBP1 gene are an uncommon cause of retinal degeneration in humans. The phenotype produced by RLBP1 mutations seems to be a form of retinitis punctata albescens.  (+info)

Retinaldehyde, also known as retinal, is a form of vitamin A that is essential for vision. It is the aldehyde form of retinol (vitamin A alcohol) and is involved in the visual cycle, where it plays a crucial role in the process of converting light into electrical signals that are sent to the brain.

When light hits the retina, it activates a protein called rhodopsin, which contains retinaldehyde as one of its components. This activation causes a chemical change in retinaldehyde, leading to the generation of an electrical signal that is transmitted to the brain via the optic nerve.

Retinaldehyde is also involved in other physiological processes, including the regulation of gene expression and cell growth and differentiation. It can be synthesized in the body from beta-carotene, a pigment found in fruits and vegetables, or obtained directly from animal sources such as liver, fish liver oil, and dairy products.

Retinal dehydrogenase, also known as Aldehyde Dehydrogenase 2 (ALDH2), is an enzyme involved in the metabolism of alcohol and other aldehydes in the body. In the eye, retinal dehydrogenase plays a specific role in the conversion of retinaldehyde to retinoic acid, which is an important molecule for the maintenance and regulation of the visual cycle and overall eye health.

Retinoic acid is involved in various physiological processes such as cell differentiation, growth, and survival, and has been shown to have a protective effect against oxidative stress in the retina. Therefore, retinal dehydrogenase deficiency or dysfunction may lead to impaired visual function and increased susceptibility to eye diseases such as age-related macular degeneration and diabetic retinopathy.

Aldehyde oxidoreductases are a class of enzymes that catalyze the oxidation of aldehydes to carboxylic acids using NAD+ or FAD as cofactors. They play a crucial role in the detoxification of aldehydes generated from various metabolic processes, such as lipid peroxidation and alcohol metabolism. These enzymes are widely distributed in nature and have been identified in bacteria, yeast, plants, and animals.

The oxidation reaction catalyzed by aldehyde oxidoreductases involves the transfer of electrons from the aldehyde substrate to the cofactor, resulting in the formation of a carboxylic acid and reduced NAD+ or FAD. The enzymes are classified into several families based on their sequence similarity and cofactor specificity.

One of the most well-known members of this family is alcohol dehydrogenase (ADH), which catalyzes the oxidation of alcohols to aldehydes or ketones as part of the alcohol metabolism pathway. Another important member is aldehyde dehydrogenase (ALDH), which further oxidizes the aldehydes generated by ADH to carboxylic acids, thereby preventing the accumulation of toxic aldehydes in the body.

Deficiencies in ALDH enzymes have been linked to several human diseases, including alcoholism and certain types of cancer. Therefore, understanding the structure and function of aldehyde oxidoreductases is essential for developing new therapeutic strategies to treat these conditions.

Tretinoin is a form of vitamin A that is used in the treatment of acne vulgaris, fine wrinkles, and dark spots caused by aging or sun damage. It works by increasing the turnover of skin cells, helping to unclog pores and promote the growth of new skin cells. Tretinoin is available as a cream, gel, or liquid, and is usually applied to the affected area once a day in the evening. Common side effects include redness, dryness, and peeling of the skin. It is important to avoid sunlight and use sunscreen while using tretinoin, as it can make the skin more sensitive to the sun.

Retinoids are a class of chemical compounds that are derivatives of vitamin A. They are widely used in dermatology for the treatment of various skin conditions, including acne, psoriasis, and photoaging. Retinoids can help to reduce inflammation, improve skin texture and tone, and stimulate collagen production.

Retinoids work by binding to specific receptors in the skin cells, which triggers a series of biochemical reactions that regulate gene expression and promote cell differentiation and turnover. This can help to unclog pores, reduce the appearance of fine lines and wrinkles, and improve the overall health and appearance of the skin.

There are several different types of retinoids used in skincare products, including retinoic acid, retinaldehyde, and retinol. Retinoic acid is the most potent form of retinoid and is available by prescription only. Retinaldehyde and retinol are weaker forms of retinoid that can be found in over-the-counter skincare products.

While retinoids can be highly effective for treating various skin conditions, they can also cause side effects such as dryness, irritation, and sensitivity to the sun. It is important to use retinoids as directed by a healthcare professional and to follow proper sun protection measures when using these products.

Retinol-binding proteins (RBPs) are a group of proteins found in the body that play a crucial role in transporting and delivering retinol (vitamin A alcohol) to various tissues and cells. RBPs are synthesized primarily in the liver and then secreted into the bloodstream, where they bind to retinol and form a complex called holo-RBP.

Cellular RBPs, also known as intracellular RBPs or CRBPs (cellular retinol-binding proteins), are a subclass of RBPs that function inside cells. They are responsible for transporting retinol within the cell and facilitating its conversion to retinal and then to retinoic acid, which are active forms of vitamin A involved in various physiological processes such as vision, immune function, and embryonic development.

CRBPs have a high affinity for retinol and help regulate its intracellular concentration by preventing its degradation and promoting its uptake into the cell. There are several isoforms of CRBPs, including CRBP-I, CRBP-II, CRBP-III, and CRBP-IV, each with distinct expression patterns and functions in different tissues and cells.

Overall, CRBPs play a critical role in maintaining the homeostasis of vitamin A metabolism and ensuring its proper utilization in various physiological processes.

Medical Definition of Vitamin A:

Vitamin A is a fat-soluble vitamin that is essential for normal vision, immune function, and cell growth. It is also an antioxidant that helps protect the body's cells from damage caused by free radicals. Vitamin A can be found in two main forms: preformed vitamin A, which is found in animal products such as dairy, fish, and meat, particularly liver; and provitamin A carotenoids, which are found in plant-based foods such as fruits, vegetables, and vegetable oils.

The most active form of vitamin A is retinoic acid, which plays a critical role in the development and maintenance of the heart, lungs, kidneys, and other organs. Vitamin A deficiency can lead to night blindness, dry skin, and increased susceptibility to infections. Chronic vitamin A toxicity can cause nausea, dizziness, headaches, coma, and even death.

Aldehyde dehydrogenase (ALDH) is a class of enzymes that play a crucial role in the metabolism of alcohol and other aldehydes in the body. These enzymes catalyze the oxidation of aldehydes to carboxylic acids, using nicotinamide adenine dinucleotide (NAD+) as a cofactor.

There are several isoforms of ALDH found in different tissues throughout the body, with varying substrate specificities and kinetic properties. The most well-known function of ALDH is its role in alcohol metabolism, where it converts the toxic aldehyde intermediate acetaldehyde to acetate, which can then be further metabolized or excreted.

Deficiencies in ALDH activity have been linked to a number of clinical conditions, including alcohol flush reaction, alcohol-induced liver disease, and certain types of cancer. Additionally, increased ALDH activity has been associated with chemotherapy resistance in some cancer cells.

Alcohol oxidoreductases are a class of enzymes that catalyze the oxidation of alcohols to aldehydes or ketones, while reducing nicotinamide adenine dinucleotide (NAD+) to NADH. These enzymes play an important role in the metabolism of alcohols and other organic compounds in living organisms.

The most well-known example of an alcohol oxidoreductase is alcohol dehydrogenase (ADH), which is responsible for the oxidation of ethanol to acetaldehyde in the liver during the metabolism of alcoholic beverages. Other examples include aldehyde dehydrogenases (ALDH) and sorbitol dehydrogenase (SDH).

These enzymes are important targets for the development of drugs used to treat alcohol use disorder, as inhibiting their activity can help to reduce the rate of ethanol metabolism and the severity of its effects on the body.

Retinol-binding proteins (RBPs) are specialized transport proteins that bind and carry retinol (vitamin A alcohol) in the bloodstream. The most well-known and studied RBP is serum retinol-binding protein 4 (RBP4), which is primarily produced in the liver and circulates in the bloodstream.

RBP4 plays a crucial role in delivering retinol to target tissues, where it gets converted into active forms of vitamin A, such as retinal and retinoic acid, which are essential for various physiological functions, including vision, immune response, cell growth, and differentiation. RBP4 binds to retinol in a 1:1 molar ratio, forming a complex that is stable and soluble in the bloodstream.

Additionally, RBP4 has been identified as an adipokine, a protein hormone produced by adipose tissue, and has been associated with insulin resistance, metabolic syndrome, and type 2 diabetes. However, the precise mechanisms through which RBP4 contributes to these conditions are not yet fully understood.

Retinoic acid receptors (RARs) are a type of nuclear receptor proteins that play crucial roles in the regulation of gene transcription. They are activated by retinoic acid, which is a metabolite of vitamin A. There are three subtypes of RARs, namely RARα, RARβ, and RARγ, each encoded by different genes.

Once retinoic acid binds to RARs, they form heterodimers with another type of nuclear receptor called retinoid X receptors (RXRs). The RAR-RXR complex then binds to specific DNA sequences called retinoic acid response elements (RAREs) in the promoter regions of target genes. This binding event leads to the recruitment of coactivator proteins and the modification of chromatin structure, ultimately resulting in the activation or repression of gene transcription.

Retinoic acid and its receptors play essential roles in various biological processes, including embryonic development, cell differentiation, apoptosis, and immune function. In addition, RARs have been implicated in several diseases, such as cancer, where they can act as tumor suppressors or oncogenes depending on the context. Therefore, understanding the mechanisms of RAR signaling has important implications for the development of novel therapeutic strategies for various diseases.

Vitamin A deficiency (VAD) is a condition that occurs when there is a lack of vitamin A in the diet. This essential fat-soluble vitamin plays crucial roles in vision, growth, cell division, reproduction, and immune system regulation.

In its severe form, VAD leads to xerophthalmia, which includes night blindness (nyctalopia) and keratomalacia - a sight-threatening condition characterized by dryness of the conjunctiva and cornea, with eventual ulceration and perforation. Other symptoms of VAD may include Bitot's spots (foamy, triangular, white spots on the conjunctiva), follicular hyperkeratosis (goose bump-like bumps on the skin), and increased susceptibility to infections due to impaired immune function.

Vitamin A deficiency is most prevalent in developing countries where diets are often low in animal source foods and high in plant-based foods with low bioavailability of vitamin A. It primarily affects children aged 6 months to 5 years, pregnant women, and lactating mothers. Prevention strategies include dietary diversification, food fortification, and supplementation programs.

Alcohol dehydrogenase (ADH) is a group of enzymes responsible for catalyzing the oxidation of alcohols to aldehydes or ketones, and reducing equivalents such as NAD+ to NADH. In humans, ADH plays a crucial role in the metabolism of ethanol, converting it into acetaldehyde, which is then further metabolized by aldehyde dehydrogenase (ALDH) into acetate. This process helps to detoxify and eliminate ethanol from the body. Additionally, ADH enzymes are also involved in the metabolism of other alcohols, such as methanol and ethylene glycol, which can be toxic if allowed to accumulate in the body.

The rhombencephalon is a term used in the field of neuroanatomy, which refers to the most posterior region of the developing brain during embryonic development. It is also known as the hindbrain and it gives rise to several important structures in the adult brain.

More specifically, the rhombencephalon can be further divided into two main parts: the metencephalon and the myelencephalon. The metencephalon eventually develops into the pons and cerebellum, while the myelencephalon becomes the medulla oblongata.

The rhombencephalon plays a crucial role in several critical functions of the nervous system, including regulating heart rate and respiration, maintaining balance and posture, and coordinating motor movements. Defects or abnormalities in the development of the rhombencephalon can lead to various neurological disorders, such as cerebellar hypoplasia, Chiari malformation, and certain forms of brainstem tumors.

The pigment epithelium of the eye, also known as the retinal pigment epithelium (RPE), is a layer of cells located between the photoreceptor cells of the retina and the choroid, which is the vascular layer of the eye. The RPE plays a crucial role in maintaining the health and function of the photoreceptors by providing them with nutrients, removing waste products, and helping to regulate the light that enters the eye.

The RPE cells contain pigment granules that absorb excess light, preventing it from scattering within the eye and improving visual acuity. They also help to create a barrier between the retina and the choroid, which is important for maintaining the proper functioning of the photoreceptors. Additionally, the RPE plays a role in the regeneration of visual pigments in the photoreceptor cells, allowing us to see in different light conditions.

Damage to the RPE can lead to various eye diseases and conditions, including age-related macular degeneration (AMD), which is a leading cause of vision loss in older adults.

Gene expression regulation, enzymologic refers to the biochemical processes and mechanisms that control the transcription and translation of specific genes into functional proteins or enzymes. This regulation is achieved through various enzymatic activities that can either activate or repress gene expression at different levels, such as chromatin remodeling, transcription factor activation, mRNA processing, and protein degradation.

Enzymologic regulation of gene expression involves the action of specific enzymes that catalyze chemical reactions involved in these processes. For example, histone-modifying enzymes can alter the structure of chromatin to make genes more or less accessible for transcription, while RNA polymerase and its associated factors are responsible for transcribing DNA into mRNA. Additionally, various enzymes are involved in post-transcriptional modifications of mRNA, such as splicing, capping, and tailing, which can affect the stability and translation of the transcript.

Overall, the enzymologic regulation of gene expression is a complex and dynamic process that allows cells to respond to changes in their environment and maintain proper physiological function.

The retina is the innermost, light-sensitive layer of tissue in the eye of many vertebrates and some cephalopods. It receives light that has been focused by the cornea and lens, converts it into neural signals, and sends these to the brain via the optic nerve. The retina contains several types of photoreceptor cells including rods (which handle vision in low light) and cones (which are active in bright light and are capable of color vision).

In medical terms, any pathological changes or diseases affecting the retinal structure and function can lead to visual impairment or blindness. Examples include age-related macular degeneration, diabetic retinopathy, retinal detachment, and retinitis pigmentosa among others.

In situ hybridization (ISH) is a molecular biology technique used to detect and localize specific nucleic acid sequences, such as DNA or RNA, within cells or tissues. This technique involves the use of a labeled probe that is complementary to the target nucleic acid sequence. The probe can be labeled with various types of markers, including radioisotopes, fluorescent dyes, or enzymes.

During the ISH procedure, the labeled probe is hybridized to the target nucleic acid sequence in situ, meaning that the hybridization occurs within the intact cells or tissues. After washing away unbound probe, the location of the labeled probe can be visualized using various methods depending on the type of label used.

In situ hybridization has a wide range of applications in both research and diagnostic settings, including the detection of gene expression patterns, identification of viral infections, and diagnosis of genetic disorders.

Developmental gene expression regulation refers to the processes that control the activation or repression of specific genes during embryonic and fetal development. These regulatory mechanisms ensure that genes are expressed at the right time, in the right cells, and at appropriate levels to guide proper growth, differentiation, and morphogenesis of an organism.

Developmental gene expression regulation is a complex and dynamic process involving various molecular players, such as transcription factors, chromatin modifiers, non-coding RNAs, and signaling molecules. These regulators can interact with cis-regulatory elements, like enhancers and promoters, to fine-tune the spatiotemporal patterns of gene expression during development.

Dysregulation of developmental gene expression can lead to various congenital disorders and developmental abnormalities. Therefore, understanding the principles and mechanisms governing developmental gene expression regulation is crucial for uncovering the etiology of developmental diseases and devising potential therapeutic strategies.

"Body patterning" is a general term that refers to the process of forming and organizing various tissues and structures into specific patterns during embryonic development. This complex process involves a variety of molecular mechanisms, including gene expression, cell signaling, and cell-cell interactions. It results in the creation of distinct body regions, such as the head, trunk, and limbs, as well as the organization of internal organs and systems.

In medical terminology, "body patterning" may refer to specific developmental processes or abnormalities related to embryonic development. For example, in genetic disorders such as Poland syndrome or Holt-Oram syndrome, mutations in certain genes can lead to abnormal body patterning, resulting in the absence or underdevelopment of certain muscles, bones, or other structures.

It's important to note that "body patterning" is not a formal medical term with a specific definition, but rather a general concept used in developmental biology and genetics.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Isoelectric focusing (IEF) is a technique used in electrophoresis, which is a method for separating proteins or other molecules based on their electrical charges. In IEF, a mixture of ampholytes (molecules that can carry both positive and negative charges) is used to create a pH gradient within a gel matrix. When an electric field is applied, the proteins or molecules migrate through the gel until they reach the point in the gradient where their net charge is zero, known as their isoelectric point (pI). At this point, they focus into a sharp band and stop moving, resulting in a highly resolved separation of the different components based on their pI. This technique is widely used in protein research for applications such as protein identification, characterization, and purification.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

A mammalian embryo is the developing offspring of a mammal, from the time of implantation of the fertilized egg (blastocyst) in the uterus until the end of the eighth week of gestation. During this period, the embryo undergoes rapid cell division and organ differentiation to form a complex structure with all the major organs and systems in place. This stage is followed by fetal development, which continues until birth. The study of mammalian embryos is important for understanding human development, evolution, and reproductive biology.

High-performance liquid chromatography (HPLC) is a type of chromatography that separates and analyzes compounds based on their interactions with a stationary phase and a mobile phase under high pressure. The mobile phase, which can be a gas or liquid, carries the sample mixture through a column containing the stationary phase.

In HPLC, the mobile phase is a liquid, and it is pumped through the column at high pressures (up to several hundred atmospheres) to achieve faster separation times and better resolution than other types of liquid chromatography. The stationary phase can be a solid or a liquid supported on a solid, and it interacts differently with each component in the sample mixture, causing them to separate as they travel through the column.

HPLC is widely used in analytical chemistry, pharmaceuticals, biotechnology, and other fields to separate, identify, and quantify compounds present in complex mixtures. It can be used to analyze a wide range of substances, including drugs, hormones, vitamins, pigments, flavors, and pollutants. HPLC is also used in the preparation of pure samples for further study or use.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

Immunohistochemistry (IHC) is a technique used in pathology and laboratory medicine to identify specific proteins or antigens in tissue sections. It combines the principles of immunology and histology to detect the presence and location of these target molecules within cells and tissues. This technique utilizes antibodies that are specific to the protein or antigen of interest, which are then tagged with a detection system such as a chromogen or fluorophore. The stained tissue sections can be examined under a microscope, allowing for the visualization and analysis of the distribution and expression patterns of the target molecule in the context of the tissue architecture. Immunohistochemistry is widely used in diagnostic pathology to help identify various diseases, including cancer, infectious diseases, and immune-mediated disorders.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

The liver is a large, solid organ located in the upper right portion of the abdomen, beneath the diaphragm and above the stomach. It plays a vital role in several bodily functions, including:

1. Metabolism: The liver helps to metabolize carbohydrates, fats, and proteins from the food we eat into energy and nutrients that our bodies can use.
2. Detoxification: The liver detoxifies harmful substances in the body by breaking them down into less toxic forms or excreting them through bile.
3. Synthesis: The liver synthesizes important proteins, such as albumin and clotting factors, that are necessary for proper bodily function.
4. Storage: The liver stores glucose, vitamins, and minerals that can be released when the body needs them.
5. Bile production: The liver produces bile, a digestive juice that helps to break down fats in the small intestine.
6. Immune function: The liver plays a role in the immune system by filtering out bacteria and other harmful substances from the blood.

Overall, the liver is an essential organ that plays a critical role in maintaining overall health and well-being.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

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