bile acid

Aldo-Keto Reductase Family 1 Member C2 (AKR1C2) plays a role in concert with the 5-α/5-β-Steroid Reductases to convert Steroid hormones into the 3-α/5-α and 3-α/5-β-Tetrahydrosteroids. AKR1C2 catalyzes the inactivation of the most potent androgen 5-α-Dihydrotestosterone (5-α-DHT) to 5-α-Androstane-3-α, 17-β-diol (3-α-diol).

Fatty Acid-Binding Protein 6 (FABP6) is cytoplasmic protein that binds long-chain fatty acids and other hydrophobic ligands which belongs to the calycin superfamily. FABP6 expression is restricted in the small intestine to the ileum where it is involved in the enterohepatic circulation of bile acids. FABP6 forms a beta-barrel structure that accommodates the hydrophobic ligand in its interior. Isoform 2 is expressed in colorectal adenocarcinomas and their adjacent normal mucosa (at protein level). Isoform 1 is expressed in the jejunum, ileum, cecum and ascending colon intestine. FABP6 plays a role in fatty acid uptake, transport, and metabolism. FABP6 stimulates gastric acid and pepsinogen secretion. It seems to be able to bind to bile salts and bilirubins.

GBA2 Protein, Rat, Recombinant (His) is expressed in E. coli expression system with C-6xHis tag. The predicted molecular weight is 42.6 kDa and the accession number is Q5M868.

Gastrotropin, also known as Fatty acid-binding protein 6, Ileal lipid-binding protein, ILBP, Intestinal 15 kDa protein, Intestinal bile acid-binding protein, I-BABP and FABP6, is a cytoplasm protein which belongs to thecalycin superfamily and Fatty-acid binding protein (FABP) family. Isoform2 of FABP6 is expressed in colorectal adenocarcinomas and their adjacent normal mucosa (at protein level). Isoform1of FABP6 is expressed in the jejunum, ileum, cecum and ascending colon intestine. Isoform2is expressed in the gallbladder, duodenum, jejunum, ileum, cecum, ascending, transverse and descending colon, sigmoid colon and rectum. FABP6 / I-BABP is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. FABP6 / I-BABP may also play an important role in early carcinogenesis.

Probably part of a deoxycholate transport system. Its expression in the presence of deoxycholate in a ygiS deletion mutant increases intracellular deoxycholate levels and decreases cell growth; higher expression in the presence of deoxycholate inhibits cell growth completely. Bile acid detergents such as deoxycholate are important for host defense against bacterial growth in the gall bladder and duodenum.

It protects esophageal epithelia from hydrogen peroxide-induced oxidative stress. It suppresses acidic bile acid-induced reactive oxigen species (ROS) and protects against oxidative DNA damage and double-strand breaks. GPX7 Protein, Mouse, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 26.7 kDa and the accession number is Q99LJ6.

Aldo-keto reductases comprise of AKR1C1-AKR1C4, four enzymes that catalyze NADPH dependent reductions and have been implicated in biosynthesis, intermediary metabolism, and detoxification. there is a strong correlation between the expression levels of these family members and the malignant transformation as well as the resistance to cancer therapy. Type I human hepatic 3alpha-hydroxysteroid dehydrogenase (AKR1C4) plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism.

Fatty acid-binding protein, liver, also known as Fatty acid-binding protein 1, Liver-type fatty acid-binding protein, FABP1 and FABPL,is a cytoplasm protein which belongs to thecalycin superfamily and Fatty-acid binding protein (FABP) family. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. FABP1 and FABP6 (the ileal fatty acid binding protein) are also able to bind bile acids. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. FABP1 / FABPL binds free fatty acids and their coenzyme A derivatives, bilirubin, and some other small molecules in the cytoplasm. It forms a beta-barrel structure that accommodates hydrophobic ligands in its interior. FABP1 / FABPL may be involved in intracellular lipid transport.

AKR1C2 is a member of the aldo/keto reductase superfamily, which consists of more than 4 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme binds bile acid with high affinity, and shows minimal 3-alpha-hydroxysteroid dehydrogenase activity. AKR1C2 gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 1p15-p14. Three transcript variants encoding two different isoforms have been found for AKR1C2 gene.

Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression.

FGF19, also known as FGF-19, is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF19 interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL, KLB and heparan sulfate glycosaminoglycans that function as coreceptors. It interacts with KL and KLB directly. However, it interacts with FGFR4 in the presence of heparin, KL or KLB. FGF19 is involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. It also stimulates glucose uptake in adipocytes.

Acyl-coenzyme A: cholesterol acyltransferase (ACAT) is an intracellular enzyme that produces cholesteryl esters in various tissues. In mammals, two ACAT genes (ACAT1 and ACAT2) have been identified. Together, these two enzymes are involved in storing cholesteryl esters as lipid droplets, in macrophage foam-cell formation, in absorbing dietary cholesterol, and in supplying cholesteryl esters as part of the core lipid for lipoprotein synthesis and assembly. The key difference in tissue distribution of ACAT1 and ACAT2 between humans, mice and monkeys is that, in adult human liver (including hepatocytes and bile duct cells), the major enzyme is ACAT1, rather than ACAT2. There is compelling evidence implicating a role for ACAT1 in macrophage foam-cell formation, and for ACAT2 in intestinal cholesterol absorption.Ubiquitin linkage to cysteine is an unconventional modification targeting protein for degradation. However, the physiological regulation of cysteine ubiquitylation is still mysterious. Here we found that ACAT2, a cellular enzyme converting cholesterol and fatty acid to cholesteryl esters, was ubiquitylated on Cys277 for degradation when the lipid level was low. gp78-Insigs catalysed Lys48-linked polyubiquitylation on this Cys277. A high concentration of cholesterol and fatty acid, however, induced cellular reactive oxygen species (ROS) that oxidized Cys277, resulting in ACAT2 stabilization and subsequently elevated cholesteryl esters. Furthermore, ACAT2 knockout mice were more susceptible to high-fat diet-associated insulin resistance. By contrast, expression of a constitutively stable form of ACAT2 (C277A) resulted in higher insulin sensitivity. ACAT2 is an appealing target for therapy to reduce coronary heart disease.

Fibroblast growth factor 19 (FGF19) is a secreted protein which belongs to the FGFs family. FGF19 is expressed in fetal brain, cartilage, retina, and adult gall bladder. FGFs modulate cellular activity via at least 5 distinct subfamilies of high-affinity FGF receptors (FGFRs): FGFR-1, -2, -3, and -4, all with intrinsic tyrosine kinase activity. FGFRs can be important for regulation of glucose and lipid homeostasis. FGF19 has important roles as a hormone produced in the ileum in response to bile acid absorption. It has been shown to cause resistance to diet-induced obesity and insulin desensitization and to improve insulin, glucose, and lipid profiles in diabetic rodents. FGF19 can be considered as a regulator of energy expenditure.