Pathways

Leucine degradation is a key metabolic process that converts the essential amino acid leucine into energy and intermediate molecules used in various biosynthetic pathways.This pathway includes several enzymatic steps that ultimately transform leucine into acetyl-CoA and acetoacetate, both of which are crucial for the tricarboxylic acid (TCA) cycle and fatty acid synthesis. These reactions not only contribute to the organism's energy production but also provide necessary building blocks for the synthesis of vital compounds.

L-lyxose is a sugar and a monosaccharide containing five carbon atoms and aldehyde group. Wild-type E.coli can't utilize L-lyxose as its source of carbon and energy. In mutated E.coli, it can metabolize l-lyxose through utilization of enzymes of the rhamnose, arabinose and 2,3-diketo-L-gulonate systems. β-L-lyxopyranose enter cell by L-rhamnose-proton symporter, then convert to l-xylulose by L-rhamnose isomerase. L-xylulose is further metabolized to L-xylulose-5-phosphate with energy ATP. Putative L-ribulose-5-phosphate 3-epimerase can convert L-xylulose -5-phosphate to L-ribulose 5-phosphate, and L-ribulose 5-phosphate 4-epimerase can catalyze L-ribulose 5-phosphate to xylulose 5-phosphate for further pentose phosphate.

L-threonine is degrade into methylglyoxal (pyruvaldehyde) by first reacting with a NDA dependent threonine dehydrogenase resulting in the release of a hydrogen ion, an NADH and a 2-amino-3-oxobutanoate. The latter compound reacts spontaneously with a hydrogen ion resulting in the release of a carbon dioxide and a aminoacetone. The aminoacetone in turn reacts with an oxygen and a water molecule through an aminoacetone oxidase resulting in the release of a hydrogen peroxide, ammonium and a methylglyoxal which can then be incorporated in the methylglyoxal degradation pathways.

Labetalol (also known as Albetol or Ibidomide) is an inhibitor/antagonist of beta-1 adrenergic receptor that can be used for treating high blood pressure and reducing cardiac output. Labetalol can bind to beta-1 adrenergic receptor on both vascular smooth muscle, which lead to inhibition of vasoconstriction in peripheral blood vessels and adrenergic stimulation of endothelial cell function.

Labetalol is a non-selective beta blocker and is a racemic mixture of 2 diastereoisomers . It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, labetalol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, labetalol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like labetalol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Labetalol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.

Labetalol is a non-selective beta blocker and is a racemic mixture of 2 diastereoisomers . It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, labetalol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, labetalol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like labetalol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Labetalol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis. Labetalol can be found under the brand name Trandate, and some side effects of using this drug may include dizziness, headaches, and stomach pain.

The lac operon in E. coli produces three proteins that are used to metabolize lactose in the absence of glucose. If glucose is present in the cell, cAMP levels will be low, and only a small amount will be able to bind to the cAMP-activated global transcriptional regulator (CRP or CAP). Without cAMP bound, the protein is unactivated, and cannot bind to the activator binding site of the operon. However, when glucose levels are low, cAMP levels are higher, and more can bind to and activate CRP, allowing it to activate the operon. At the same time, if lactose levels in the cell are low, there will be minimal amounts of allolactose produced by any beta-galactosidase present currently in the cell. Allolactose is necessary to bind to the lactose operon repressor, and without allolactose bound to the repressor, it is tightly bound to the operator region of the operon. However, when concentrations of lactose are higher in the cell, more allolactose is produced, and when it binds to the repressor, the repressor cannot bind to the operator, freeing it and allowing RNA polymerase to bind. This, combined with the binding of the CRP protein to the activator binding site leads to all three genes in the operon being transcribed. The first gene, lacZ, encodes the protein beta-galactosidase, an enzyme that hydrolyzes beta-galactosides into monosaccharides. In this instance, it hydrolyzes lactose into glucose and galactose. In some cases, it can also cause the isomerization of lactose into allolactose. The second gene, lacY, encodes the protein lactose permease, which is a transport protein that pumps lactose into the cell by using a proton gradient that also flows into the cell. Finally, the last gene, lacA, encodes the protein galactoside O-acetyltransferase, an enzyme that catalyzes the transfer of the acetyl group of acetyl-CoA to beta-galactosides. This specific protein is not known to be important to the lac operon, but may be important in detoxifying the bacteria by preventing acetylated galactosides from re-entering the cell.