Pantothenic Acid in the Treatment of Obesity

Pantothenic Acid and Weight Reduction

With pantothenic acid so closely related to lipid metabolism, the question is raised if it has anything to do with obesity, and hence weight reduction. In the rest of this article, we will explore the problem of weight reduction which is an equally, if not more mysterious problem than acne vulgaris.

Regarding negative calorie balance and dieting, the only guiding principle behind weight reduction is that the calorie intake must be less than the calorie output, so that there is a negative calorie balance. The body will try to make up for this negative balance by burning the fat that is stored in the fat cells, the so-called depot fat. In this process, fat in the body is consumed, and the individual loses weight. This sounds rather simple and the goal should therefore easily be achieved. In practice, however, this is quite a different story. By taking in less than what is actually needed, the dieter in fact faces two hurdles that may prove too difficult to overcome. There is the problem of hunger. It takes enormous self-restraint and determination to keep the appetite in check and when hungry there is the constant temptation to satiate this primitive instinct by grabbing whatever is available. To keep this situation in check is difficult, but not insurmountable with a conscious effort, conviction and perseverance. But more troublesome and difficult to manage is the weakness, sweating, dizziness and fainting episodes that follow the sensation of hunger. Under such circumstances, the dieter will have little choice except to start eating again, gaining back the weight that he has tried so hard to shed.

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Pantothenic Acid in the Treatment of Acne Vulgaris “A Medical Hypothesis”

The Pathogenesis of Acne Vulgaris: A Medical Hypothesis

Over the years the pathogenesis of acne vulgaris has been extensively studied including, the structure and function of the pilosebaceous follicle, the physiology of sebum, microflora in acne vulgaris, and abnormal follicular keratinization, considered to be one of the earliest events in acne formation. Despite the concerted effort of many scientists, internists, pathologists and dermatologists, the pathogenesis of acne vulgaris remains largely elusive.

In this paper, I would like to approach this problem from a different perspective. My clinical observations suggest that acne vulgaris may be closely related to the consumption of diets, which are rich in fat content. This impression is by no means novel. Textbooks do briefly mention this correlation though, more often than not, it is dismissed as irrelevant. However, my observations have led to quite the contrary conclusions. Not only is the fat content of food closely related to acne vulgaris but it forms some sort of linear relationship with the disease process. The more fat the patient consumes, the more severe will be the acne process. This observation is in line with the opinion of many dermatologists that chocolate, which is composed mainly of the creamy part of milk, and has a high degree of fat content, is bad for acne.

Significantly, in this group of patients, any deliberate attempt in trying to avoid a fatty diet over a period of weeks, if not days, will often result in important compound, cholesterol, which in turn is basically synthesized from units of acetyl-CoA. In the synthetic process, the body naturally is always trying not only to reach for a normal level of androgens, but an optimal level, so as to allow the body to function at its best. However, this is not always possible, and the normal level reached may not represent the optimal level. This is natures flexible way of dealing with shortage of essential dietary elements in any form to achieve a level that is just enough to manage the present situation, leaving a variable degree of shortage from the optimal level. In the present instance, in the two groups of boys, one group may have a normal level of androgens that is falling short of the optimum. One possible explanation for this is that there is a lack of basic building blocks, the acetyl-CoAs, which deter the body from operating at peak efficiency. If this is a viable possibility,

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Pantethine Clinical Studies and Research

Pantethine: A review of its biochemistry and therapeutic applications

Pantethine is the stable disulfate form of pantetheine, the metabolic substrate which constitutes the active part of Coenzyme-A (CoA) molecules and acyl carrier proteins. Because pantethine is located nearer to Coenzyme-A than is pantothenic acid in the biosynthetic pathway of Coenzyme-A, it has been suggested it will have clinical benefits in conditions where pantothenic acid is not effective, and clinical trials with pantethine appear to prove this argument. Oral administration of pantethine has consistently shown an ability to favorably impact a variety of lipid risk factors in persons with hypercholesterolemia, arteriosclerosis, and diabetes. Pantethine administration positively affects parameters associated with platelet lipid composition and cell membrane fluidity. (Alt. Med. Rev. 1997;2(5):365-377)

Pantethine, which is known to be converted to Coenzyme-A, has been reported to have antiarrhythmic action on experimental cardiac arrhythmias

Using standard microelectrode techniques, the electrophysiological effects of pantethine under hypoxic (95% N2 + 5% CO2) perfusion were studied. Hypoxia decreased resting membrane potential, action potential amplitude and maximum velocity of phase 0 and shortened action potential duration and effective refractory period. Application of pantethine 5 X 10(-3) Gm/ml under hypoxic perfusion prolonged action potential duration and effective refractory period significantly. Prolongation of action potential duration by pantethine might be caused by an increase in intracellular ATP. The findings in this study could be an explanation of the possible antiarrhythmic effects of pantethine. Hayashi H, Kobayashi A, Terada H, Nagao B, Nishiyama T, Kamikawa T, Yamazaki N. Effects of pantethine on action potential of canine papillary muscle during hypoxic perfusion. In: Jpn Heart J (1985 Mar) 26(2):289-96.

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Fatty Acid Synthesis and Modification

Coenzyme-A is a commonly used carrier for activated acyl groups (acetyl, fatty acyl and others). The thioester bond, which links the acyl group to Coenzyme-A, has a large negative standard free energy of hydrolysis (-7.5 kcal/mole). This qualifies it as a high energy bond, and explains why an acyl group attached to Coenzyme-A in this manner is considered to be activated.

The fatty acid (1) obtained from fat digestion is converted into the thioester of Coenzyme-A (2) by an acyl CoA synthetase enzyme. The complete structure of Coenzyme-A is shown above and is commonly abbreviated as HSCoA. The first step of the b-oxidation cycle involves dehydrogenation of 2 to give the a,b-unsaturated thioester.

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Formation of Acetyl Coenzyme-A

Summary: Pyruvate is degraded and combined with Coenzyme-A to form acetyl coenzyme A; hydrogens are released; and carbon dioxide is released.

The pyruvic molecules formed in glycolosis enter the mitochondria, where they are converted to acetyl Coenzyme-A (acetyl-CoA). In this complex series of reactions, pyruvate undergoes oxidative decarboxylation. First, a carboxyl group is removed as carbon dioxide, which diffuses out of the cell. Then the two-carbon fragment remaining is oxidized, and the hydrogens that were removed during the oxidation are accepted by NAD+. Finally, the oxidized two-carbon fragment, an acetyl group, is attached to Coenzyme-A, which is manufactured in the cell from one of the B vitamins, pantothenic acid. The reaction is catalyzed by a multienzyme complex that contains several copies of each of three different enzymes. The overall reaction for the formation of acetyl Coenzyme-A can be stated as follows:

2 pyruvate + 2 NAD+ + 2 CoA —-> 2 acetyl-CoA + 2 NADH + 2 carbon dioxide

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Cellular Respiration

Overview

Living organisms catabolize organic molecules within their cells and use the energy released to manufacture ATP by phosphorylating ADP. Many prokaryotes and virtually all eukaryotes phosphorylate ADP either through fermentation (anaerobic) or respiration (aerobic). Both of these processes involve oxidation of foodstuffs, yet only the latter requires oxygen.

The Role of Coenzymes

In metabolic pathways, coenzymes play a vital role. Metabolic enzymes operate in the body’s cells and blood. Metabolic enzymes facilitate the chemical reactions that carry out the processes of metabolism. Typically, metabolic enzymes are composed of two components: (1) an “apoenzyme” that identifies which molecule within a cell requires a specific chemical reaction and (2) a “coenzyme” that initiates the specific chemical reaction.

The body’s primary sources of energy are produced at the cellular level by metabolic processes. Coenzyme-A (CoA), Acetyl Coenzyme-A (acetyl CoA), Coenzyme Q10 (CoQ10) and Coenzyme 1 (NADH), together with certain B-vitamins and their coenzyme forms are necessary for such energy production during: (1) the tricarboxylic acid cycle (the TCA cycle, Krebs cycle, or citric acid cycle) and (2) the glycolitic cycle.

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Energy from Fatty Acid and Glucose

Many cellular processes require energy. Most of these reactions are enzymatically coupled to another, energy liberating, reaction. Coenzyme-A is required to initiate the body’s energy cycle (known variously as the ATP, TCA, Krebs, or citric acid cycle), it is constantly expended and constantly needs replenishing. Coenzyme-A converts metabolic energy sources, like sugars and fats into cellular energy. Coenzyme-A also helps the cells deliver fuel to the ATP cycle: carbohydrate from anaerobic (insufficient oxygen in the system) metabolism and fat from aerobic (sufficient oxygen) metabolism.

Coenzyme-A is manufactured in the cells of the body from three components: adenosine triphosphate (ATP), cysteine, and pantothenic acid (vitamin B-5). Pantothenic acid is the primary cofactor of Coenzyme-A; however, it will pass out of the body without manufacturing Coenzyme-A unless sufficient adenosine triphosphate (ATP) and cysteine are both available.

Nicotinamide adenine dinucleotide (NADH)

Nicotinamide adenine dinucleotide (NADH), plays a central role in oxidative metabolism. Through the mitochondrial electron transport chain, NADH can transfer two electrons and a hydrogen ion to oxygen, liberating 52.6 kcal/mole. This is enough energy to synthesize 7.2 ATPs from ADP and Pi. However, if Coenzyme-A is not available in sufficient amounts then the human body cannot fully utilize NADH and many of the other nutrients it needs to stay healthy.

Energy from Fatty Acids

Fat molecules consist of three fatty acid chains connected by a glycerol backbone. Fatty acids are basically long chains of carbon and hydrogen and are the major source of energy during normal activities.

Fatty acids are broken down by progressively cleaving two carbon bits and converting these to acetyl Coenzyme-A. The acetyl CoA is then oxidized by the same citric acid cycle involved in the metabolism of glucose. For every two carbons in a fatty acid, oxidation yields 5 ATPs generating the acetyl CoA and 12 more ATPs oxidizing the coenzyme. This makes fat a terrific molecule in which to store energy, as the body well knows (much to our dismay).

The only biological drawback to this, and other, forms of oxidative metabolism is its dependence on oxygen. Thus, if energy is required more rapidly than oxygen can be delivered, muscles switch to the less efficient anaerobic pathways. Interestingly, this implies that an anaerobic workout will not “burn” any fat, but will preferentially deplete the body of glucose. Of course, your body can’t survive very long on just anaerobic metabolism…it just can’t generate enough energy.

Energy from Glucose

Two different pathways are involved in the metabolism of glucose: one anaerobic and one aerobic. The anaerobic process occurs in the cytoplasm and is only moderately efficient. The aerobic cycle takes place in the mitochondria and is results in the greatest release of energy. As the name implies, though, it requires oxygen.

Anaerobic metabolism

Glucose in the bloodstream diffuses into the cytoplasm and is locked there by phosphorylation. A glucose molecule is then rearranged slightly to fructose and phosphorylated again to fructose diphosphate. These steps actually require energy, in the form of two ATPs per glucose. The fructose is then cleaved to yield two glyceraldehyde phosphates (GPs). In the next steps, energy is finally released, in the form of two ATPs and two NADHs, as the GPs are oxidized to phosphoglycerates. One of the key enzymes in this process is glyceraldehyde phosphate dehydrogenase (GPDH), which transfers a hydrogen atom from the GP to NAD to yield the energetic NADH. Due to its key position in the glycolytic pathway, biochemical assays of GPDH are often used to estimate the glycolytic capacity of a muscle cell. Finally, two more ATPs are produced as the phosphoglycerates are oxidized to pyruvate.

Aerobic metabolism

Pyruvate is the starting molecule for oxidative phosphorylation via the Krebb’s, TCA or citric acid cycle. In this process, all of the C-C and C-H bonds of the pyruvate will be transferred to oxygen. The pathway can be seen in the figure below.

The Krebs Cycle

The Krebs cycle is also known as the TCA cycle or the Citric Acid cycle. It is used primarily for production of energy at the cellular level via production of ATP. These reactions occur in the mitochondria. The Krebs cycle can use fatty acids, proteins and glucose for energy production.

Coenzyme-A (CoA) is required to begin the cycle. Oxidized pyruvate combines with Coenzyme-A to yield Acetyl Coenzyme-A. One molecule of Acetyl-CoA produces 1 molecule of ATP (from GTP), 1 molecule of FADH2, and 3 molecules of NADH.

Next, Coenzyme-A delivers the acetyl group to oxaloacetate (OXA), a four carbon compound already present in the mitochondrion, with which the 2 carbon acetyl group combines to form citric acid. This step initiates the “first turn” of the Krebs cycle. At the end of the Krebs cycle, oxaloacetate has once again been formed. A second Acetyl-CoA combines with it, initiating the second turn of the Krebs cycle.

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