Pathways

The loop of Henle of the nephron can be separated into an ascending limb and the descending limb. The descending limb is highly impermeable to solutes such as sodium, but permeable to water. Conversely, the ascending limb is highly impermeable to water, but permeable to solutes. Chloride, potassium, and sodium are co-transported across the apical membrane (closest to the lumen) via transporters from the filtrate. The transporter requires all three ions present to be effective and to maintain electroneutrality. In addition, the three ions are transported across the basolateral membrane (closest to the renal interstitium) via other means such as the sodium potassium ATPase transports and the chloride channels in the membrane. As these solutes are being actively transported out of the ascending limb and into the renal interstitium/capillary network without water following (due to the lack of water permeability), the filtrate becomes more diluted. Furthermore, these ions simultaneously causes an increase in osmotic pressure that contributes to water reabsorption in the descending limb. This effect can be magnified with the help of vasopressin, which is a hormone that is typically involved with water reabsorption. However, when it acts on the ascending limb, it aids in increasing sodium reabsorption which will increase water reabsorption in the latter parts of the nephron (the distal tubule and collecting duct).

The collecting duct of the nephron is the last segment of the functioning nephron and is connected to minor calyces and the ensuing renal pelvis of the kidney where urine continues before it is stored in the bladder. The collecting duct is mainly responsible for the excretion and reabsorption of water and ions. It is composed of two important cell types: intercalated cells that are responsible for maintaining acid-base homeostasis, and principal cells that help maintain the body's water and salt balance. When renin is released from the kidneys, it causes the activation of angiotensin I in the blood circulation which is cleaved to become angiotensin II. Angiotensin II stimulates the release of aldosterone from the adrenal cortex and release of vasopressin from the posterior pituitary gland. When in the circulation, vasopressin eventually binds to receptors on epithelial cells in the collecting ducts. This causes vesicles that contain aquaporins to fuse with the plasma membrane. Aquaporins are proteins that act as water channels once they have bound to the plasma membrane. As a result, the permeability of the collecting duct changes to allow for water reabsorption back into the blood circulation. In addition, sodium and potassium are also reabsorbed back into the systemic circulation at the collecting duct via potassium and sodium channels. However, aldosterone is a major regulator of the reabsorption of these ions as well, as it changes the permeability of the collective duct to these ions. As a result, a high concentration of sodium and potassium in the blood vessels occurs. Some urea and other ions may be reabsorbed as well. The reabsorption of ions and water increases blood fluid volume and blood pressure.

The loop of Henle of the nephron can be separated into an ascending limb and the descending limb. The ascending limb is highly impermeable to water, but permeable to solutes. Conversely, the descending limb is highly impermeable to solutes such as sodium, but permeable to water. As solutes are being actively transported out of the ascending limb, the solutes cause in increase in osmotic pressure. This, combined with the ability for water to move freely out of the descending limb, leads to a water reabsorption into the adjacent capillary network and a high concentration of sodium in the filtrate at the descending Limb. Water moves from the descending loop to the capillary network through aquaporin channels in the cell membrane.

The distal convoluted tubule of the nephron is the part of the kidney between the loop of henle and the collecting duct. When renin is released from the kidneys, it causes the activation of angiotensin I in the blood circulation which is cleaved to become angiotensin II. Angiotensin II stimulates the release of aldosterone from the adrenal cortex and release of vasopressin from the posterior pituitary gland. When in the circulation, vasopressin eventually binds to receptors on epithelial cells in the distal convoluted tubule. This causes vesicles that contain aquaporins to fuse with the plasma membrane. Aquaporins are proteins that act as water channels once they have bound to the plasma membrane. As a result, the permeability of the distal convoluted tubule changes to allow for water reabsorption back into the blood circulation. In addition, sodium, chlorine, and calcium are also reabsorbed back into the systemic circulation via their respective channels and exchangers. However, aldosterone is a major regulator of the reabsorption of these ions as well, as it changes the permeability of the distal convoluted tubule to these ions. As a result, a high concentration of sodium, chlorine, and calcium in the blood vessels occurs. The reabsorption of ions and water increases blood fluid volume and blood pressure.

The proximal convoluted tubule is part of the nephron between the Bowman's capsule and the loop of Henle. The proximal convoluted tubule functions to reabsorb sodium, water, and other ions. Sodium and bicarbonate (hydrogen carbonate) are transported by a co-transporter that is responsible for the majority of sodium reabsorption. The bicarbonate, along with hydrogen, are exchanged across the basal and apical membranes, respectively, to effectively regulate the pH of the filtrate. In addition, chloride ions are not normally reabsorbed in large amounts at the proximal tubule compared to other parts of the nephron. However, the reabsorption of chloride, as well as potassium, increases as the amount of water reabsorption increases due to solvent drag (also known as bulk transport). This occurrence explains solute movement secondary to water flow. All the cation and anion transport creates a gradient favourable for ion and water reabsorption, leading to an increase in blood pressure.

Metabolites of Kinetin are predicted with biotransformer.

Krabbe disease, also called globoid cell leukodystrophy, is an extremely rare inherited inborn error of metabolism (IEM). It is a degenerative disorder that affects the nervous system. It has an estimated prevalence of 1/100,000 in the Northern European population and a worldwide incidence of 1/100,000-1/250,000 live births. Krabbe disease is an autosomal recessive disorder that is caused by a deficiency of an enzyme called galactosylceramidase. Galactosylceramidase is a lysosomal protein that hydrolyzes the galactose ester bonds of ceramides and ceramide derivatives including galactocerebroside, galactosylsphingosine (psychosine), lactosylceramide, and monogalactosyldiglyceride. More specifically, galactosylceramidase is an enzyme that is involved in the catabolism (via the removal of galactose) of galactosylceramide, a major lipid in myelin, kidney, and epithelial cells of the small intestine and colon. Defects in galactosylceramidase lead to the accumulation of cytotoxic psychosine, which ultimately leads to apoptosis of oligodendrocytes and demyelination. As a result, this enzyme deficiency impairs the growth and maintenance of myelin, the protective sheath around nerve cell axons that ensures that electrical impulses are rapidly transmitted. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). Krabbe disease is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that often have multiple nuclei. There are three different phenotypes for Krabbe disease: infantile, juvenile, and late-onset. Neurodegeneration and early death (at age 2-3) occur in most infantile cases. In juvenile patients, the disease is often fatal 2-7 years after the symptoms begin. Adult-onset patients can survive many years after symptoms first manifest. The symptoms of infantile Krabbe disease usually begin during the first year of life. Typically, the initial signs and symptoms include feeding difficulties, episodes of fever without any sign of infection, irritability, stiff posture, muscle weakness, and slowed mental and physical development. Muscles continue to weaken as the disease progresses which decreases the infant's ability to move, chew, swallow, and breathe. It is also common for affected infants to experience vision loss and seizures. Treatment is limited to hematopoietic stem cell transplantation in pre-symptomatic infantile patients and mildly affected late-onset patients. Stem cell transplants have been shown to slow the progression of the disease.

Krabbe disease, also called globoid cell leukodystrophy, is an extremely rare inherited inborn error of metabolism (IEM). It is a degenerative disorder that affects the nervous system. It has an estimated prevalence of 1/100,000 in the Northern European population and a worldwide incidence of 1/100,000-1/250,000 live births. Krabbe disease is an autosomal recessive disorder that is caused by a deficiency of an enzyme called galactosylceramidase. Galactosylceramidase is a lysosomal protein that hydrolyzes the galactose ester bonds of ceramides and ceramide derivatives including galactocerebroside, galactosylsphingosine (psychosine), lactosylceramide, and monogalactosyldiglyceride. More specifically, galactosylceramidase is an enzyme that is involved in the catabolism (via the removal of galactose) of galactosylceramide, a major lipid in myelin, kidney, and epithelial cells of the small intestine and colon. Defects in galactosylceramidase lead to the accumulation of cytotoxic psychosine, which ultimately leads to apoptosis of oligodendrocytes and demyelination. As a result, this enzyme deficiency impairs the growth and maintenance of myelin, the protective sheath around nerve cell axons that ensures that electrical impulses are rapidly transmitted. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). Krabbe disease is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that often have multiple nuclei. There are three different phenotypes for Krabbe disease: infantile, juvenile, and late-onset. Neurodegeneration and early death (at age 2-3) occur in most infantile cases. In juvenile patients, the disease is often fatal 2-7 years after the symptoms begin. Adult-onset patients can survive many years after symptoms first manifest. The symptoms of infantile Krabbe disease usually begin during the first year of life. Typically, the initial signs and symptoms include feeding difficulties, episodes of fever without any sign of infection, irritability, stiff posture, muscle weakness, and slowed mental and physical development. Muscles continue to weaken as the disease progresses which decreases the infant's ability to move, chew, swallow, and breathe. It is also common for affected infants to experience vision loss and seizures. Treatment is limited to hematopoietic stem cell transplantation in pre-symptomatic infantile patients and mildly affected late-onset patients. Stem cell transplants have been shown to slow the progression of the disease.

Krabbe disease, also called globoid cell leukodystrophy, is an extremely rare inherited inborn error of metabolism (IEM). It is a degenerative disorder that affects the nervous system. It has an estimated prevalence of 1/100,000 in the Northern European population and a worldwide incidence of 1/100,000-1/250,000 live births. Krabbe disease is an autosomal recessive disorder that is caused by a deficiency of an enzyme called galactosylceramidase. Galactosylceramidase is a lysosomal protein that hydrolyzes the galactose ester bonds of ceramides and ceramide derivatives including galactocerebroside, galactosylsphingosine (psychosine), lactosylceramide, and monogalactosyldiglyceride. More specifically, galactosylceramidase is an enzyme that is involved in the catabolism (via the removal of galactose) of galactosylceramide, a major lipid in myelin, kidney, and epithelial cells of the small intestine and colon. Defects in galactosylceramidase lead to the accumulation of cytotoxic psychosine, which ultimately leads to apoptosis of oligodendrocytes and demyelination. As a result, this enzyme deficiency impairs the growth and maintenance of myelin, the protective sheath around nerve cell axons that ensures that electrical impulses are rapidly transmitted. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). Krabbe disease is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that often have multiple nuclei. There are three different phenotypes for Krabbe disease: infantile, juvenile, and late-onset. Neurodegeneration and early death (at age 2-3) occur in most infantile cases. In juvenile patients, the disease is often fatal 2-7 years after the symptoms begin. Adult-onset patients can survive many years after symptoms first manifest. The symptoms of infantile Krabbe disease usually begin during the first year of life. Typically, the initial signs and symptoms include feeding difficulties, episodes of fever without any sign of infection, irritability, stiff posture, muscle weakness, and slowed mental and physical development. Muscles continue to weaken as the disease progresses which decreases the infant's ability to move, chew, swallow, and breathe. It is also common for affected infants to experience vision loss and seizures. Treatment is limited to hematopoietic stem cell transplantation in pre-symptomatic infantile patients and mildly affected late-onset patients. Stem cell transplants have been shown to slow the progression of the disease.