ANDROPATHY
 R.A.S HEMAT, MB;BCh, FRCSI, Dip.Urol.UCL.
Andropathy is defined as any disease or condition that affects only males. Proteins in a cell may be normal or abnormal, and both must be degraded at one time or another. Normal proteins are more or less stable and long-lived, depending on their type and role. Proteins that regulate gene transcription, cell cycle and division, DNA repair, and metabolic pathways are needed temporarily and are short-lived. There are several causes for the presence of abnormal proteins inside a cell. Stress tends to denature most proteins, even if they are structurally normal. Free radicals has an unpaired electron in an outer orbit. The energy generated by this unstable atomic state is released via reactions with surrounding molecules, which results in molecular damage. The mechanisms available to the cell for counteracting the effects of ROS are varied.
- Under anaerobic conditions, protoporphyrinogen oxidase is obligatory coupled to the cell’s anaerobic respiratory chain. Any compound that can serve as a terminal electron acceptor (e.g., nitrate) in this chain permits the oxidation of porphrinogen. Aerobic organisms produce the bulk of their ATP by the oxidation of reduced substrates coupled to the phosphorylation of ADP to ATP, with oxygen serving as the terminal electron acceptor. Oxygen transport is optimised by tight regulation of ventilation and the red cell mass.
- Enzymatic adaptation to hyperoxia depends on the upregulation of appropriate genes that detoxify ROS. Most ligands, including polypeptide hormones and growth factors (erythropoietin), and variety of smaller molecules (catecholamines, steroids, thyroid hormones), act solely as messengers, having no function independent of their interaction with receptor. Oxygen is known to bind to and react with heme proteins.There is a chemical link between alterations in intracellular oxygen concentration and responsive changes in the structure and function of appropriate transcription factors. The most logical and best-worked out mechanism for such signalling is by means of oxidation-reduction (redox) modification of protein sulfydryl groups.Regulation of angiogenesis is critical in development and also in adaptation to episodes of local hypoxia. Effective wound healing depends on the proliferation of new blood vessels to maintain an adequate supply of oxygen and nutrients to the metabolically active repair tissue. Angiogenesis plays a critical role in the pathogenesis of a variety of pathological states ranging from cancer to diabetic and sickle cell retinopathies.
The effect of hypoxia on expression of glycolytic enzymes varies among cell types and may contribute to stress adaptation. The mitochondrial permeability transition (MPT) is characterised by a sudden increase in the permeability of the mitochondrial inner membrane to small ions and molecules, leading to complete collapse of the membrane potential and colloid-osmotic swelling of mitochondrial matrix.Under pathological conditions MPT can be a source of irreversible injury. Swollen mitochondria are hallmark of cells undergoing necrosis.Ischaemia/reperfusion injury is a complex phenomenon involving cell-to-cell interactions, tissue architecture, and zonal structure, as well as changes in individual cells. Mitochondrial permeability transition (MPT) leads to necrotic and apoptotic cell death as a result of ischaemia/reperfusion.After ATP depletion that can be caused by hypoxia, ischaemia or hypoglycaemia there may be complete recovery, death, or secondary damage (about 7 days after the initial ATP depletion).Heat shock proteins (HSP), are synthesised after hypoxia.
Most people find it difficult to maintain exercise regimens for long periods of time. The activity of adenosine monophosphate-activated kinase (AMPK) is increased by muscle contraction as well as other factors that increase the ratio of AMP to ATP in the cell, i.e., energy sensor. Short-duration exercise of varying intensities increases AMPK activity. Adipocyte depots comprise a key endocrine organ. Adiponectin is an adipocyte-secreted insulin-sensitising and anti-atherosclerotic hormone. Plasma adiponectin levels correlate inversely with adiposity and fasting blood glucose levels and low adiponectin levels may precede declines in insulin sensitivity in humans.Adiponectin is initially synthesised by adipocytes in an inactive, high-molecular-weight form.Following insulin receptor binding and signal transduction, glucose transporters are recruited from the intracellular pool to the plasma membrane, exposing functional glucose transporters to the extracellular medium containing glucose. There is intercellular communication between adipose and muscle cells.A consistent weigh-training program produces gains in muscle strength and muscle size.Both the physical damage caused as well as the metabolic depletion can lead to an altered cellular calcium balance during and after exercise.
Muscular dysfunctional of 30-50%, reduction of muscle endurance, diminished muscles tone, and increased fatigability are common features of ageing and muscle injury. Muscle response to nervous stimulation is decreased with decreased muscle norepinephrine. One sucrose (white sugar) molecule is one glucose bonded to one fructose. Fructose decreases the ATP content of the liver. The liver is the chief metabolic organ of the body, uses 12% of the body’s total ATP. The first 3 pillars of ageing excess insulin, cortisol and blood glucose are all interlocking and mutually enhancing. Adenylate cyclase enzyme produces the cAMP second messenger inside the cell. Insulin opposes cAMP production by adenylate cyclase. Insulin is one of the few hormones (cortisol being the other major one), which increases with age. Walking provides the body with an alternative method to remove excess glucose from the bloodstream without the usual need for insulin secretion. Obesity is a reflection of increased enlarged fat stores, in both subcutaneous and visceral fat deposits.Leptin is a cytokine, derived primarily from fat cells, but also from the placenta and possibly the stomach, reduces food intake and increases the activity of the thermogenic components of the sympathetic nervous system. Obesity may be related to abnormal levels of dopamine, and exercise may increase dopamine.
April, 2007
The information in this article has been excerpted from the following books: ANDROPATHY, by R.A.S. HEMAT.
Note: Permission is granted to copy and redistribute this document electronically as long as it is unmodified. This article may not be sold in any medium, including electronic, CD-ROM, or database, or published in print, without the explicit, written permission of Dr. R. A. S. Hemat.
Clinical Orthomolecularism Classroom
Dr. R.A.S HEMAT declares no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, stock holdings, gifts, or honoraria.
Since 2000
© Urotext
|
