Pathways

Lactose synthesis occurs only in the mammary glands, producing lactose (4-O-B-D-galactosylpyranosyl-a-D-glucopyranoside), the major sugar in milk. Lactose is created by joining two monosaccarides with a B1,4 glycosidic bond. Glucose is first converted to UDP-galactose via the enzyme galactose-1-phosphate uridylyltransferase. UDP-galactose is then transported into the Golgi by the UDP galactose translocator, an antiporter which uses facilitated transport to move UDP galactose into the Golgi and exports UMP. Once inside the Golgi, the UDP galactose and glucose (which moves into the golgi via the GLUT-1 transporter) become substrates for the lactose synthase enzyme complex, comprised of the enzymatic subunit, galactosyltransferase with its regulatory subunit, Alpha-lactalbumin. Lactose synthase creates lactose through bonding galactose from UDP to glucose through a glycosidic bond. Although GT is found in many tissues in the body, Alpha-lactalbumin is only found on the inner surface of the Golgi in the mammary glands, limiting lactose production to the mammaries.

Lactose synthesis occurs only in the mammary glands, producing lactose (4-O-B-D-galactosylpyranosyl-a-D-glucopyranoside), the major sugar in milk. Lactose is created by joining two monosaccarides with a B1,4 glycosidic bond. Glucose is first converted to UDP-galactose via the enzyme galactose-1-phosphate uridylyltransferase. UDP-galactose is then transported into the Golgi by the UDP galactose translocator, an antiporter which uses facilitated transport to move UDP galactose into the Golgi and exports UMP. Once inside the Golgi, the UDP galactose and glucose (which moves into the golgi via the GLUT-1 transporter) become substrates for the lactose synthase enzyme complex, comprised of the enzymatic subunit, galactosyltransferase with its regulatory subunit, Alpha-lactalbumin. Lactose synthase creates lactose through bonding galactose from UDP to glucose through a glycosidic bond. Although GT is found in many tissues in the body, Alpha-lactalbumin is only found on the inner surface of the Golgi in the mammary glands, limiting lactose production to the mammaries.

Lactulose is a disaccharide derivative of lactose used to treat constipation and portal systemic encephalopathy. Lactulose is indicated for use as a laxative in the treatment of chronic constipation in adults and geriatric patients. Additionally, lactulose is also employed as an adjunct to protein restriction and supportive therapy for the prevention and treatment of portal-systemic encephalopathy (PSE), including both the hepatic pre-coma and coma variations. In particular, lactulose solution has been effective at managing PSE resulting from surgical portacaval shunts or from chronic hepatic diseases like cirrhosis. Lactulose formulations are most commonly administered via the oral route or the rectal route. Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut. In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea. The human small intestinal mucosa does not have the enzymes to split lactulose, and hence lactulose reaches the large bowel unchanged. Lactulose is metabolized in the colon by colonic bacteria to monosaccharides, and then to volatile fatty acids, hydrogen, and methane. Lactulose reduces intestinal ammonia production and absorption in three ways. First, the colonic metabolism of sugars causes a laxative effect via an increase in intraluminal gas formation and osmolality which leads to a reduction in transit time and intraluminal pH. This laxative effect is also beneficial for constipation. Next, lactulose promotes increased uptake of ammonia by colonic bacteria which utilize the trapped colonic ammonia as a nitrogen source for protein synthesis. The reduction of intestinal pH facilitates this process, which favors the conversion of ammonia (NH3) produced by the gut bacteria, to ammonium (NH4+), an ionized form of the molecule, unable to cross biological membranes. Finally, lactulose also causes a reduction in intestinal production of ammonia. The acidic pH destroys urease-producing bacteria involved in the production of ammonia. The unabsorbed disaccharide also inhibits intestinal glutaminase activity, which blocks the intestinal uptake of glutamine, and its metabolism to ammonia. As one of the principal features of PSE involves the accumulation of nitrogenous waste products like ammonia in the systemic circulation, a state in which the colonic contents become more acidic than blood allows ammonia in the circulation to diffuse into the colon.

Lafutidine (also known as INN) is a second generation histamine H2 receptor antagonist that can be used for treating ulcers and reflux. Inhibition of histamine H2 receptor can inhibit histamine-stimulated gastric acid secretion which will lead to reduced gastric volume and acidity.

Lamivudine (also known as 3TC) is an antiretroviral drug that can be used to treat HIV/AIDS. Lamivudine is phosphorylated to lamivudine triphosphate (L-TP), which is its active metabolite. Lamivudine triphosphate (L-TP) can bind and inhibit the HIV reverse transcriptase as well as HBV polymerase, which lead to DNA chain termination.

Lamivudine is a reverse transcriptase inhibitor used to treat HIV and hepatitis B infections. It is a nucleoside reverse transcriptase inhibitor (NRTI) that targets HIV infected cells in the body. When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell. Lamivudine enters the cell via solute carrier family 22 member 2 and is converted into lamivudine monophosphate by deoxycytidine kinase. UMP-CMP kinase protein then converts lamivudine monophosphate into lamivudine diphosphate. The lamivudine diphosphate is metabolized to lamivudine triphosphate via nucleoside diphosphate kinase A or phosphoglycerate kinase 1. Limuvudine triphosphate is an analog of deoxycytidine-5'-triphosphate (dCTP). Lamivudine triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dCTP and by incorporation into viral DNA. Lamivudine triphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once lamivudine triphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed. Common side effects from taking lamivudine include headache, nausea, vomiting, diarrhea, weight loss, abdominal pain, fever, cough and nasal signs & symtpoms.

Lamivudine (2'-deoxy-3'-thiacytidine, 3TC) is a pyrimidine analog reverse transcriptase enzyme inhibitor used to treat human immunodeficiency virus type I (HIV-1), HIV-2, and Hepatitis B. When metabolized to its active triphosphate form, it competes with deoxycytidine triphosphate for binding to reverse transcriptase, resulting in chain termination when incorporated into the viral DNA. Lamivudine may enter the cells by passive diffusion or by active transported via SLC22A1, SLC22A2, and SLC22A3. Intracellularly, it is phosphorylated to its active triphosphate from via deoxycytidine kinase (3TC to 3TC-monophosphate), followed by cytidine monophosphate/deoxycytidine monophosphate kinase (3TC-monophosphate to 3TC-diphosphate), then 3'-phosphoglycerate kinase or nucleoside diphosphate kinase (3TC-diphosphate to 3TC-triphosphate). Dephosphorylation can occur via phosphatases or salvage pathways. Lamivudine is actively transported out of cell by efflux transporters ABCB1, ABCC1, ABCC2, ABCC3, ABCC4 and ABCG2 and primarily excreted unchanged in the urine.