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valeric acid side chain (Figure 9.19). Biotin’s structure was first determined by Kogl (from Europe) and by
du Vigeaud and coworkers (from the United States) in the early 1940s, but the vitamin’s discovery
occurred earlier. Biotin’s discovery
was based on the research investigating the cause of what was called “egg white injury.” Eating raw eggs
was known to result in hair loss, dermatitis, and various neuromuscular problems. Szent-Györgyi in 1931
found a substance (now called biotin) in liver that could cure and prevent the condition. Biotin was once
called vitamin H (the H refers to haut in German and means “skin”) as well as vitamin B7.
SOURCES Sources of biotin for humans include biotin in dietary foods as well as biotin made by intestinal
bacteria living within the large intestine. Biotin is found widely distributed in foods. Good food sources
of the vitamin include liver, soybeans, and egg yolk, as well as cereals, legumes, and nuts. Within many
foods, biotin is found either bound covalently to protein or as biocytin, which consists of biotin bound
to the amino acid lysine. Biocytin is also sometimes called biotinyllysine (Figure 9.20). One substance in
raw egg whites, avidin, has been found to bind biotin and prevent its absorption and use by the body.
Avidin is a glycoprotein and irreversibly binds biotin in what has been suggested as the tightest
noncovalent bond found in nature. The binding between avidin and biotin in turn prevents biotin
absorption. Yet, because avidin is heat-labile (unstable with heat), eating cooked egg whites does not
compromise biotin absorption.
can be further hydrolyzed by other proteases or peptidases within the small intestine, and biocytin can
be further hydrolyzed by biotinidase. Biotinidase is found on the intestinal brush border as well as in
pancreatic and intestinal juices secreted into the small intestine. The enzyme hydrolyzes the biocytin to
release free biotin and lysine. Some undigested biocytin may be absorbed intact by peptide carriers and
subsequently hydrolyzed by biotinidase present in plasma or in most other body tissues. Any absorbed
biocytin not catabolized by biotinidase is excreted in the urine. Biotinidase is active over a wide pH
range and is specific for the biotinyl moiety [1–4]. It is found in most body cells, and its activity is
expressed in multiple cellular locations including the nucleus [3,4]. At a more acidic pH, the enzyme
biotinidase cleaves biocytin to produce biotin and lysine, or cleaves covalently bound biotin from any
biotinyl peptides that have been released as biotinylated proteins are degraded within various cells of
the body. The enzyme also cleaves biotin from histones. At a more alkaline pH, the enzyme has been
shown to become biotinylated while also generating free lysine; in other words, the biotinidase enzyme
becomes attached to the biotin that was previously part of biocytin. Biotinidase deficiency (first
discovered in 1983) is caused by an autosomal recessive inborn error of metabolism. Should infants and
children with the disorder go untreated, a biotin deficiency, among other problems, develops. Some
clinical features associated with the genetic disorder include seizures, ataxia, skin rash, alopecia (hair
loss), and acidosis [1,2]. Free biotin is absorbed primarily in the jejunum, followed by the ileum, because
of differences in carrier concentrations [5]. Dietary biotin is thought to be nearly completely absorbed,
although alcohol can inhibit biotin absorption [6]. Biotin that is synthesized by colonic bacteria is
absorbed in the proximal and midtransverse colon; however, bacterially made biotin cannot totally meet
the biotin needs of humans [5]. The mechanism of biotin absorption varies with intake. Biotin
absorption occurs by passive diffusion with consumption of pharmacologic doses. With physiological
biotin intakes, biotin absorption across the brush border membrane of the small intestine and across the
colonocytes is carrier mediated and sodium dependent. The main carrier for biotin found in the small
intestine as well as the
iver (among other tissues) also transports pantothenic acid and lipoic acid and is called the sodium-
dependent multivitamin transporter (SMVT) [5,7,8]. Another transporter of biotin that is widely
expressed in tissues is from the solute carrier gene family 19 (SLC19A3); this carrier transports both
thiamin and biotin [9]. Transport of biotin across the basolateral membrane of the enterocyte is carrier
mediated, but not sodium dependent [5]. Biotin is found in the plasma mostly (about 80%) in a free,
unbound state, with lesser amounts bound to protein. In the blood, albumin and α- and β-globulins bind
biotin, as does biotinidase, which has two binding sites for biotin and arises from hepatic secretion [10].
Biotin uptake into the liver, and probably other tissues, is thought to involve SMVT as well as other
carriers. Two biotin transporters found in leukocytes include monocarboxylate transporter (MCT) 1 and
another carrier from solute carrier family 19 member 3 (SLC19A3) [9,11]. Biotin is stored in small
quantities in the muscle, liver, and brain [12].
FUNCTIONS AND MECHANISMS OF ACTION Biotin functions in cells covalently bound to enzymes and
thus is considered a coenzyme. In addition, biotin functions in non-coenzyme roles including possible
roles in cell proliferation and gene expression. Coenzyme Roles For coenzyme functions within cells,
biotin is attached (covalently bound) to four carboxylases. The attachment of biotin to these enzymes
occurs in two steps and is cata
lyzed by the enzyme holocarboxylase synthetase, which is found in the cytoplasm and mitochondria. In
the first step of the synthesis of the carboxylases, biotin reacts with ATP in a Mg21-dependent reaction
to form biotinyl adenosine monophosphate (also called activated biotin) and pyrophosphate. In the
second step, the activated biotin reacts with any of four apocarboxylases to form a holoenzyme
carboxylase (sometimes called holocarboxylases or just biotin-dependent carboxylases) with the release
of AMP. A mutation in holocarboxylase synthetase, as was first discovered in 1981, or a mutation in any
of the four biotindependent carboxylases can cause problems in metabolism. The four biotin-dependent
carboxylases, which are synthesized by holocarboxylase synthetase, are acetyl CoA carboxylase,
pyruvate carboxylase, propionyl CoA carboxylase, and β-methylcrotonyl CoA carboxylase. Table 9.2 lists
these enzymes and their roles in metabolism. Knowles [13] provides detailed information on the
mechanism of action of the biotin-dependent enzymes. Each holoenzyme biotin-dependent carboxylase
is a multisubunit enzyme to which biotin is attached by an amide linkage. Specifically, the carboxyl
terminus of biotin’s valeric acid side chain is linked to the є amino group of a specified lysine residue in
the apoenzyme [14]. The chain connecting biotin and the apoenzyme is long and flexible, allowing the
biotin to move from one active site of the carboxylase to another. Figure 9.21 depicts the attachment of
biotin to the enzyme, emphasizing the long, flexible chain and the amide linkage between the vitamin
and the lysine residue of the enzyme. One active
site on the apoenzyme generates the carboxybiotin enzyme, and the other transfers the activated
carbon dioxide to a reactive carbon on the substrate. Figure 9.22 illustrates the formation of the CO2-
biotin-enzyme c omplex.
Pyruvate Carboxylase Pyruvate carboxylase is a particularly interesting and important enzyme because
of its regulatory function. Specifically, pyruvate carboxylase (a mitochondrial enzyme) catalyzes the
carboxylation of pyruvate to form oxaloacetate (Figure 9.23). For its activation, pyruvate carboxylase
requires the presence of acetyl CoA as well as ATP and Mg21. Acetyl CoA serves as an allosteric
activator, and its presence indicates the need for increased amounts of oxaloacetate. If the cell has a
surplus of ATP, the oxaloacetate is then used for gluconeogenesis. However, if the cell is deficient in
ATP, the oxaloacetate enters the TCA cycle on condensation with acetyl CoA.
Acetyl CoA Carboxylase The importance of biotin in energy metabolism is further exemplified by its role
in the initiation of fatty acid synthesis, that is, the formation
of malonyl CoA from acetyl CoA by the regulatory and rate-limiting enzyme acetyl CoA carboxylase. This
enzyme (found in both the mitochondria and cytoplasm) is allosterically activated by citrate and
isocitrate and inhibited by long-chain fatty acyl CoA derivatives. ATP and Mg21 are required for the
reaction (see Figure 5.27).
Propionyl CoA Carboxylase Propionyl CoA carboxylase (a mitochondrial enzyme) is important for the
catabolism of the amino acids isoleucine, threonine, and methionine, each of which generates propionyl
CoA. Propionyl CoA also arises from the catabolism of odd-number-chain fatty acids found, for example,
in some fish. Propionyl CoA carboxylase catalyzes the carboxylation of propionyl CoA to D-
methylmalonyl CoA (Figure 9.24). The reaction requires ATP and Mg21. Deficient or defective propionyl
CoA carboxylase activity causes the genetic disorder propionic acidemia, characterized by the
accumulation of propionyl CoA, which is then shifted into an alternate metabolic pathway. This alternate
p athway results in increased production and urinary excretion of 3-hydroxypropionic acid (3HPA) and
methylcitrate (MCA).
CSCoA
(3MCG), and isovalerylglycine (IVG) [14,15]. Increased 3-HIA and decreased biotin concentrations in the
urine are indicative of biotin deficiency [16].
Noncoenzyme Roles Although the coenzyme role of biotin is well characterized, other possible roles of
biotin are less known and investigated. Some of these roles are reviewed briefly in this section.
Cell Proliferation, Gene Silencing, and DNA Repair Biotin is hypothesized to exert effects on cell
proliferation, gene silencing, and DNA repair through its attachment to histones in the nucleus of cells.
Histones, of which there are four classes—H2A, H2B, H3, and H4—are small proteins that are bound to
or associated with DNA as part of chromatin. Histones influence multiple processes. The attachment of
biotin to histones is mediated by holocarboxylase synthetase and biotinidase. The biotinidase becomes
biotinylated (i.e., forms biotinyl biotinidase) from the biotin moiety of biocytin and then transfers the
biotin moiety to the histones at an alkaline pH [3,4,17,18]. The significance of the biotinylation is not
clear, although effects on the cell cycle have been demonstrated. Biotinylation of histones appears to
increase in response to cell proliferation. For example, mononucleated blood cells at the G1, S, G2, and
M phases of the cell cycle displayed significantly more biotinylated histones versus quiescent cells
[19,20]. In addition, biotinylation of histones has been found to affect gene slicing and cellular responses
to some DNA damage [20–22].
Gene Expression and Cell Signalling Biotin (and possibly biotin catabolites) are also known to affect gene
expression; in fact, more than 2000 human genes depend on biotin for expression [20]. Many (over 25%)
of the genes that are biotin responsive play a role in cell signalling [20]. Effects of biotin on gene
expression have been demonstrated in vitro and in animal studies. Specifically, biotin appears to be
necessary for transcription of some genes and for translation of some mRNAs [21–25]. For example,
biotin stimulates the expression (transcription) of glucokinase but inhibits the expression of
phosphoenolpyruvate carboxykinase [18,23]. Biotin also increases mRNA levels of 6-
phosphofructokinase when given to biotin-deficient rats, and mRNA levels of holocarboxylase
synthetase are reduced with biotin deficiency and then increase in response to biotin supplementation
[23]. Biotin’s effects on gene expression are mediated by various cell signals and transcription factors
such as biotinylAMP and cGMP, nuclear factors (NF)-κB, transcription factors Sp1 and Sp3, and receptor
tyrosine kinases that span cell membranes [18,20,23]. The activity of these cell signals depends on
biotin.
METABOLISM AND EXCRETION Catabolism of the biotin holocarboxylases by proteases yields biotin
oligopeptides and ultimately biocytin. The biocytin is then degraded by biotinidase to yield lysine and
free biotin. Some of this biotin is excreted intact in the urine, and some may be reused or degraded [20].
In the catabolism of biotin, little degradation of the ring system of the vitamin occurs in humans. Most
of the metabolites arise from degradation of the valeric acid side chain of biotin by β-oxidation. The
main metabolites f ollowing catabolism of this side chain are bisnorbiotin and tetranorbiotin (Figure
9.26) and, to a lesser degree, other derived metabolites such as bisnorbiotin methyl ketone and
tetranorbiotin methyl ketone [6,26]. Bisnorbiotin and tetranorbiotin, along with the other metabolites,
are excreted in the urine. Small amounts of other biotin metabolites are formed from oxidation of the
sulfur in biotin’s ring. These metabolites, which also are excreted in the urine, include biotin sulfoxide
and biotin sulfone (Figure 9.26) [6,26,27]. Smoking appears to accelerate biotin catabolism in women
[28]. Biotin that has been synthesized by intestinal bacteria but not absorbed is excreted in the feces.
Very little dietary biotin that is absorbed is excreted in the feces [5].
ADEQUATE INTAKE Because intestinally synthesized biotin is not sufficient to maintain normal biotin
status, humans need to obtain biotin from the diet. An adequate intake (AI) recommendation for adults
age 19 years and older of 30 μg biotin per day has been suggested [16]. As discussed earlier in this
chapter under pantothenic acid, an AI is used instead of an RDA when insufficient data are available to
establish an estimated average requirement (EAR) and subsequent RDA [16]. Adequate intakes for biotin
of 30 and 35 μg per day are suggested for women during pregnancy and lactation, respectively [16]. The
inside covers of this book provide additional AIs for biotin for other age groups.
TOXICITY Toxicity of biotin has not been reported, and thus no tolerable upper intake level has been
established [16]. For example, fairly large doses (100 mg or more) of biotin have been given daily to
people with inherited disorders of biotin metabolism without side effects [16]. Use of biotin as hair and
skin conditioning agents in cosmetics has also been shown to be safe [33].
ASSESSMENT OF NUTRITURE Evaluation of biotin in blood as well as in urine has most often been used
to assess biotin status. Low plasma concentrations of biotin, however, have not been shown to
accurately reflect intake or status [16]. Decreased urinary biotin excretion (<6 μg/day or <200 pg/mL)
coupled with increased urinary excretion of 3-hydroxyisovaleric acid generated from altered metabolism
of β-methylcrotonyl CoA has been shown to be a sensitive indicator of biotin deficiency [15,16]. In fact,
alterations in urinary 3-hydroxyisovaleric acid excretion, which can be detected within about 2 weeks of
ingesting a biotin-deficient diet, are thought to be a more sensitive indicator than urinary biotin
excretion [31,34].
BIOTIN
Biotin terdiri secara struktural dari dua cincin — cincin ureido yang bergabung dengan cincin
tiofena — dengan rantai samping asam valerat tambahan (Gambar 9.19). Struktur Biotin pertama
kali ditentukan oleh Kogl (dari Eropa) dan oleh du Vigeaud dan rekan kerja (dari Amerika Serikat)
pada awal 1940-an, tetapi penemuan vitamin terjadi sebelumnya. Penemuan Biotin didasarkan
pada penelitian yang menyelidiki penyebab apa yang disebut "cedera putih telur." Makan telur
mentah diketahui menyebabkan kerontokan rambut, dermatitis, dan berbagai masalah
neuromuskuler. Szent-Györgyi pada tahun 1931 menemukan zat (sekarang disebut biotin) dalam
hati yang dapat menyembuhkan dan mencegah kondisi tersebut. Biotin dulunya disebut vitamin H
(H mengacu pada haut dalam bahasa Jerman dan berarti "kulit") serta vitamin B7.
SUMBER
Sumber biotin untuk manusia termasuk biotin dalam makanan makanan serta biotin yang
dibuat oleh bakteri usus yang hidup di dalam usus besar. Biotin ditemukan banyak didistribusikan
dalam makanan. Sumber makanan vitamin yang baik termasuk hati, kedelai, dan kuning telur, serta
sereal, kacang-kacangan, dan kacang-kacangan. Dalam banyak makanan, biotin ditemukan baik
terikat secara kovalen pada protein atau sebagai biocytin, yang terdiri dari biotin yang terikat
dengan asam amino lisin. Biocytin juga kadang-kadang disebut biotinyllysine (Gambar 9.20).
Salah satu zat dalam putih telur mentah, avidin, telah ditemukan mengikat biotin dan
mencegah penyerapan dan penggunaannya oleh tubuh. Avidin adalah glikoprotein dan mengikat
biotin secara ireversibel dalam apa yang telah disarankan sebagai ikatan nonkovalen yang paling
ketat yang ditemukan di alam. Pengikatan antara avidin dan biotin pada gilirannya mencegah
penyerapan biotin. Namun, karena avidin labil panas (tidak stabil dengan panas), makan putih telur
yang dimasak tidak mengganggu penyerapan biotin.
Pyruvate Carboxylase Pyruvate carboxylase adalah enzim yang sangat menarik dan penting
karena fungsi pengaturannya. Secara khusus, piruvat karboksilase (enzim mitokondria)
mengkatalisasi karboksilasi piruvat untuk membentuk oksaloasetat (Gambar 9.23). Untuk aktivasi,
piruvat karboksilase memerlukan keberadaan asetil CoA serta ATP dan Mg21. Asetil KoA
berfungsi sebagai aktivator alosterik, dan keberadaannya menunjukkan perlunya peningkatan
jumlah oksaloasetat. Jika sel memiliki kelebihan ATP, oksaloasetat kemudian digunakan untuk
glukoneogenesis. Namun, jika sel kekurangan ATP, oksaloasetat memasuki siklus TCA pada
kondensasi dengan asetil KoA.
Asetil KoA Karboksilase Pentingnya biotin dalam metabolisme energi lebih lanjut
dicontohkan oleh perannya dalam inisiasi sintesis asam lemak, yaitu pembentukan malonil CoA
dari asetil KoA oleh enzim asetil CoA karboksilase yang mengatur dan membatasi kadar. Enzim
ini (ditemukan di kedua mitokondria dan sitoplasma) diaktifkan secara alosterik oleh sitrat dan
isocitrate dan dihambat oleh turunan lemak asil CoA rantai panjang. ATP dan Mg21 diperlukan
untuk reaksi (lihat Gambar 5.27).
Propionil CoA Karboksilase Propionil CoA karboksilase (enzim mitokondria) penting untuk
katabolisme asam amino isoleusin, treonin, dan metionin, yang masing-masing menghasilkan
propionil CoA. Propionil CoA juga muncul dari katabolisme asam lemak rantai angka ganjil yang
ditemukan, misalnya, pada beberapa ikan. Propionil CoA karboksilase mengkatalisasi karboksilasi
propionil CoA menjadi D-metilmalonil CoA (Gambar 9.24). Reaksi ini membutuhkan ATP dan
Mg21. Aktivitas propionil CoA karboksilase propionil yang kurang atau rusak menyebabkan
kelainan genetik propionik asidemia, yang ditandai dengan akumulasi propionil CoA, yang
kemudian diubah menjadi jalur metabolisme alternatif. Alternatif ini menghasilkan peningkatan
produksi dan ekskresi asam 3-hidroksipropionik (3HPA) dan metilsitrat (MCA) urin.
β-methylcrotonyl CoA Carboxylase β-methylcrotonyl CoA carboxylase penting dalam
katabolisme leusin asam amino. Selama katabolisme leusin (Gambar 9.25), β-methylcrotonyl CoA
terbentuk. Senyawa ini c-boxylated dalam ATP-, Mg21-, dan reaksi biotin-dependen oleh β-
methylcrotonyl CoA carboxylase untuk membentuk β-methylglutaconyl CoA, yang selanjutnya
dikatabolisme untuk menghasilkan asetoasetat dan asetil KoA. Aktivitas β-methylcrotonyl CoA
karboksilase yang kurang menyebabkan akumulasi β-methylcrotonyl CoA, yang kemudian
didorong ke jalur metabolisme alternatif. Jalur alternatif ini menghasilkan peningkatan produksi
dan ekskresi asam 3- hydroxyisovaleric (3-HIA) urin, 3-metylcrotonylglycine (3MCG), dan
isovalerylglycine (IVG) [14,15]. Peningkatan 3-HIA dan penurunan konsentrasi biotin dalam urin
merupakan indikasi defisiensi biotin [16].
Peran Nonkoenzim
Meskipun peran koenzim biotin ditandai dengan baik, peran biotin lainnya yang mungkin
kurang diketahui dan diselidiki. Beberapa peran ini diulas secara singkat di bagian ini.
Proliferasi Sel, Pembungkaman Gen, dan Perbaikan DNA Biotin dihipotesiskan untuk
mengerahkan efek pada proliferasi sel, pembungkaman gen, dan perbaikan DNA melalui
keterikatannya dengan histone dalam inti sel. Histon, yang terdiri dari empat kelas — H2A, H2B,
H3, dan H4 — adalah protein kecil yang terikat atau terkait dengan DNA sebagai bagian dari
kromatin. Histon mempengaruhi banyak proses. Perlekatan biotin ke histones dimediasi oleh
holocarboxylase synthetase dan biotinidase. Biotinidase menjadi terbiotinilasi (mis., Membentuk
biotinil biotinidase) dari moitas biotin biocytin dan kemudian mentransfer moitas biotin ke
histones pada pH basa [3,4,17,18]. Signifikansi biotinilasi tidak jelas, meskipun efek pada siklus
sel telah ditunjukkan. Biotinilasi histone tampaknya meningkat sebagai respons terhadap
proliferasi sel. Sebagai contoh, sel-sel darah mononukleasi pada fase G1, S, G2, dan M dari siklus
sel menunjukkan secara signifikan lebih banyak histone yang terbiotinilasi dibandingkan dengan
sel diam [19,20]. Selain itu, biotinilasi histones telah ditemukan mempengaruhi pengirisan gen dan
respon seluler terhadap beberapa kerusakan DNA [20-22].
Ekspresi gen dan pensinyalan sel Biotin Sel (dan mungkin biotin katabolit) juga diketahui
mempengaruhi ekspresi gen; pada kenyataannya, lebih dari 2000 gen manusia bergantung pada
biotin untuk ekspresi [20]. Banyak (lebih dari 25%) gen yang responsif biotin berperan dalam
pensinyalan sel [20]. Efek biotin pada ekspresi gen telah dibuktikan secara in vitro dan pada
penelitian pada hewan. Secara khusus, biotin tampaknya diperlukan untuk transkripsi beberapa
gen dan untuk penerjemahan beberapa mRNA [21-25]. Sebagai contoh, biotin menstimulasi
ekspresi (transkripsi) glukokinase tetapi menghambat ekspresi fosfoenolpiruvat karboksibase
[18,23]. Biotin juga meningkatkan kadar mRNA 6-fosfofruktokinase ketika diberikan pada tikus
yang kekurangan biotin, dan kadar mRNA dari holocarboxylase synthetase dikurangi dengan
defisiensi biotin dan kemudian meningkat sebagai respons terhadap suplementasi biotin [23]. Efek
Biotin pada ekspresi gen dimediasi oleh berbagai sinyal sel dan faktor transkripsi seperti
biotinylAMP dan cGMP, faktor nuklir (NF) -kB, faktor transkripsi Sp1 dan Sp3, dan reseptor
tirosin kinase yang merentang membran sel [18,20,23]. Aktivitas sinyal sel ini tergantung pada
biotin.
KEKURANGAN
Kekurangan biotin pada manusia ditandai oleh kelesuan, depresi, halusinasi, nyeri otot,
paresthesia pada ekstremitas, anoreksia, mual, alopecia (kerontokan rambut), dan dermatitis merah
bersisik. Selain itu, penurunan biotin plasma dan dalam beberapa aktivitas enzim yang bergantung
pada biotin, dan perubahan ekskresi biotin dalam urin dan beberapa metabolitnya terjadi [6,15,29].
Diet tanpa biotin dapat menyebabkan penurunan biotin plasma dan mengurangi ekskresi biotin
dalam waktu sekitar 2 hingga 4 minggu [30,31].
Kekurangan biotin atau status biotin yang buruk, meskipun cukup jarang, terjadi pada berbagai
populasi. Orang yang mengonsumsi telur mentah dalam jumlah berlebih cenderung mengalami
defisiensi biotin karena gangguan penyerapan biotin. Gangguan penyerapan biotin juga dapat
terjadi dengan gangguan pencernaan seperti penyakit radang usus dan achlorhydria (kekurangan
asam klorida dalam jus lambung), pada orang yang menggunakan terapi obat antikonvulsan, atau
pada konsumen kronis dari jumlah alkohol yang berlebihan. Status biotin telah terbukti menurun
pada beberapa wanita selama kehamilan [15]. Kekurangan biotin dikenal sebagai teratogenik pada
hewan [32]. Orang dengan cacat genetik yang melibatkan aktivitas biotinidase dan
holocarboxylase sintetase mengalami defisiensi biotin kecuali jika diobati dengan dosis
farmotologis biotin. Suplemen biotin dalam jumlah 5 hingga 10 mg setiap hari digunakan untuk
mengobati defisiensi biotinidase, dan dosis 40 hingga 100 mg biotin setiap hari efektif pada orang
dengan defisiensi holocarboxylase synthetase [2].
TOKSISITAS
Toksisitas biotin belum dilaporkan, dan dengan demikian tidak ada tingkat asupan atas yang
dapat ditoleransi [16]. Sebagai contoh, dosis yang cukup besar (100 mg atau lebih) dari biotin telah
diberikan setiap hari kepada orang-orang dengan kelainan bawaan metabolisme biotin tanpa efek
samping [16]. Penggunaan biotin sebagai agen pengkondisi rambut dan kulit dalam kosmetik juga
terbukti aman [33].
PENILAIAN GIZI
Evaluasi biotin dalam darah dan juga dalam urin paling sering digunakan untuk menilai status
biotin. Konsentrasi biotin plasma yang rendah, bagaimanapun, belum terbukti secara akurat
mencerminkan asupan atau status [16].
Penurunan ekskresi biotin urin (<6 μg / hari atau <200 pg / mL) ditambah dengan peningkatan
ekskresi asam 3-hidroksiisovalerik urin yang dihasilkan dari perubahan metabolisme β-
methylcrotonyl CoA telah terbukti menjadi indikator sensitif defisiensi biotin [15, 16]. Faktanya,
perubahan dalam ekskresi asam 3-hidroksiisovalerat urin, yang dapat dideteksi dalam waktu
sekitar 2 minggu setelah mengkonsumsi diet yang kekurangan biotin, dianggap sebagai indikator
yang lebih sensitif daripada ekskresi biotin urin [31,34].