Aug 29, 2012


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Coenzyme Q10 (CoQ 10) or ubiquinone is essentially a vitamin or vitamin-like substance. Disagreements on nomenclature notwithstanding, vitamins are defined as organic compounds essential in minute amounts for normal body function acting as coenzymes or precursors to coenzymes. They are present naturally in foods and sometimes are also synthesized in the body. CoQ10 likewise is found in small amounts in a wide variety of foods and is synthesized in all tissues. The biosynthesis of CoQ10 from the amino acid tyrosine is a multistage process requiring at least eight vitamins and several trace elements. Coenzymes are cofactors upon which the comparatively large and complex enzymes absolutely depend for their function. Coenzyme Q10 is the coenzyme for at least three mitochondrial enzymes (complexes I, II and III) as well as enzymes in other parts of the cell. Mitochondrial enzymes of the oxidative phosphorylation pathway are essential for the production of the high-energy phosphate, adenosine triphosphate (ATP), upon which all cellular functions depend. The electron and proton transfer functions of the quinone ring are of fundamental importance to all life forms; ubiquinone in the mitochondria of animals, plastoquinone in the chloroplast of plants, and menaquinone in bacteria. The term "bioenergetics" has been used to describe the field of biochemistry looking specifically at cellular energy production. In the related field of free radical chemistry, CoQ10 has been studied in its reduced form (Fig. 1) as a potent antioxidant. The bioenergetics and free radical chemistry of CoQ10 are reviewed in Gian Paolo Littarru's book, Energy and Defense, published in 1994(1). Read more here
Book here
Coenzyme Q10 (CoQ10) is naturally produced by the body and is an important factor in aerobic cellular respiration. This substance plays key roles in cellular energy production in mitochondria and is a potent antioxidant. The productivity of CoQ10 declines during the aging process. The heart, liver and kidneys have the highest energy requirements, thus these organs have the highest concentrations of CoQ10. Significant decreases in levels of CoQ10 are observed in various diseases such as diabetes, congestive heart failure, myocardial infarction, and cancer. Emerging evidence supports that administration of CoQ10 may have beneficial effects at the mitochondrial level. This review will emphasize the cellular mechanisms of CoQ10 and the administration of CoQ10 in different clinical disease states.

Mitochondria and Coenzyme Q10

Anatomy of mitochondria

The structure of a mitochondrion is unique as it contains two double-layer phospholipid membranes.11 Figure 1 presents the structural characteristics of a mitochondrion and illustrates CoQ10 or ubiquinone. The two double-layer phospholipid membranes are the outer and inner membrane respectively, which are embedded with proteins and enzymes. Similar to the membranes of other organelles, the outer membrane of the mitochondrion encloses the whole organelle. Relatively large internal channels are formed by many integral proteins in the outer membrane to allow passage of molecules. Distinguished from the outer membrane, the mitochondrial inner membrane forms many folds known as cristae. The surface area of the inner membrane is increased substantially, thus enhancing the productivity of cellular respiration. The outer and inner membranes divide the mitochondrion into two compartments, the intermembrane space and the mitochondrial matrix. The area between the outer and inner membranes is called the intermembrane space. The mitochondrial matrix is the compartment enclosed by the inner membrane. There are various enzymes, mitochondrial ribosomes, deoxyribonucleic acid (DNA), and granules within the matrix. Coenzyme Q10 or ubiquinone is located on the electron transport chain in the inner membrane, a key component in adenosine triphosphate (ATP) production.

                      Figure 1. Anatomic Structure of a Mitochondrion Illustrating Ubiquinone (Coenzyme Q10).
DNA: deoxyribonucleic acid
Figure 1. Anatomic Structure of a Mitochondrion Illustrating Ubiquinone (Coenzyme Q10).

The roles of coenzyme Q10 in mitochondrial ATP and ROS production

The uniqueness of the mitochondrion in the cells result from its essential function in the survival and apoptosis of cells.12 Adenosine triphosphate, the primary molecular energy required for vital organs like the brain, heart, lungs, skeletal muscles, and kidneys, is mainly generated in the mitochondria by converting digested nutrients such as proteins, lipids, and carbohydrates via oxidative phosphorylation. Oxidative phosphorylation begins when carbohydrates are metabolized into glucose and then into pyruvate in the cytoplasm via glycolysis. The pyruvate is transported into the mitochondrion and formed into acetyl CoA where it enters the citric acid cycle, resulting in NADH and FADH2. This process decreases equivalents utilized for transporting electrons. Figure 2 demonstrates the key roles of CoQ10 in mitochondrial bioenergetics and mitochondrial ROS reduction involving the five mitochondrial complexes (I, II, III, IV, and V) in the electron transport chain. As shown in Figure 2, the electron transport chain is located on the mitochondrial inner membrane. Complexes I and II are the sites for oxidation of NADH and FADH2, respectively. Coenzyme Q10 is located between complexes I, II and III, and functions as an electron transporter. Electrons generated during oxidation are transported by CoQ10 from complexes I and II to complex III. In complex III, electrons are transferred to cytochrome c. In complex IV, oxygen receives electrons from cytochrome c, generating water. An electrochemical gradient is created during electron transport as the protons being pumped across the inner membrane into the intermembrane space from the matrix. At complex V, ATP synthase utilizes the energy from the electrochemical gradient to condense a molecule of inorganic phosphate with adenosine diphosphate (ADP), resulting in generation of ATP. To fully utilize ATP, vital organs must have the capacity to adjust the ATP synthesis to meet metabolic requirements. In the heart, this is accomplished through an energy transfer process called the creatine kinase energy shuffle. During this mechanism, creatine kinase catalyzes the high-energy bond in ATP to form phosphocreatine. Smaller than ATP, phosphocreatine rapidly diffuses from the mitochondria to the myofibrils, whereby myofibrillar creatine kinase catalyzes the reformation of ATP from phosphocreatine. Functioning as an energy buffer, the levels of phosphocreatine decreases when cardiac metabolic demands increase, maintaining ATP levels.

                      Figure 2. Key roles of CoQ10 in mitochondrial bioenergetics and mitochondrial ROS reduction.
CoQ10: coenzyme Q10; ROS: reactive oxygen species; ATP: adenosine triphosphate; ADP: adenosine diphosphate; ANT: Adenine Nucleotide Translocase.As shown in Figure 2, mitochondrial ROS are also produced during electron transport and are natural byproducts of normal oxygen metabolism. Reactive oxygen species are a group of highly reactive molecules that contain oxygen and unpaired electrons. During the process of transporting electrons in the mitochondria, superoxide (O2 -) is generated as electrons are added to oxygen (O2). Superoxide is then converted by superoxide dismutase (SOD2) to hydrogen peroxide (H2O2), which can be further reduced to hydroxyl radicals (OH-).12 The extent of ROS formation can be significantly influenced by the functional activity of the mitochondria. For example, higher mitochondrial membrane potential and lower concentrations of ADP can lead to greater production of ROS. Hydroxyl radicals can directly and indirectly damage DNA, lipids, and proteins by oxidation. As the only endogenously synthesized lipid soluble antioxidant, the reduced form of CoQ10 (ubiquinol) can effectively protect not only lipids from peroxidation but also proteins from oxidation by reducing the initiating free radicals and preventing propagation. It can also interfere with DNA oxidation, especially mitochondrial DNA.13 The potent antioxidant property of ubiquinol presents a strong defensive mechanism against oxidative damage for all cells.With aging or various diseases, there is a significant decrease in either the biosynthesis of CoQ10 or its productivity in mitochondrial bioenergetics and scavenging ROS. Consequently, with low levels of CoQ10 there is a corresponding energetic deficiency and excessive formation of ROS with low levels of CoQ10. These abnormalities can be substantially ameliorated by exogenous CoQ10 supplementation. Excessive ROS can activate apoptotic pathways and lead to apoptosis or programmed cell death when too much damage is caused to its mitochondria.14 When the production of ROS exceeds the capacity of the antioxidant system to counterbalance, damage to protein, DNA, and lipids occurs. Oxidation of the mitochondrial outer membrane by ROS can induce mitochondrial dysfunction by destroying the membrane potential, leading to the release of cytochrome c from the mitochondria. The releasing of cytochrome c can initiate apoptotic pathway.

Figure 2. Key roles of CoQ10 in mitochondrial bioenergetics and mitochondrial ROS reduction.

Aug 28, 2012

Why Should Adults be Vaccinated?

Physician Focus: Why should adults be vaccinated?


Dr. Sandin Dr. Choi

Dr. Sandin Dr. Choi

By By Drs. Elisa Choi and Margaret Sandin
Posted Aug 28, 2012 @ 09:59 AM
Last update Aug 28, 2012 @ 10:19 A
Vaccines are some of medicine’s best preventive measures with extraordinary records of effectiveness and safety. Because of vaccines, diseases that once killed millions – such as smallpox, diphtheria, or polio - are no longer a threat to health or life.
While Americans do well in immunizing children (though many are still unprotected, as evidenced by recent outbreaks of measles and whooping cough), adults are another story.
Consider the following, from the National Foundation for Infectious Diseases:
More than 50,000 adults die each year from vaccine-preventable diseases and their complications.
More than 36,000 people die from seasonal flu complications every year; 90 percent are people 65 and older.

Some 1.25 million people are chronically infected with the hepatitis B virus, which can lead to liver cancer.
Nearly one-third of the reported cases of pertussis, or whooping cough are in adults.

Several factors contribute to this disappointing picture. When it comes to their own health, most adults appear indifferent to vaccination. They are conscientious about getting their children shots, but don’t think of vaccinations for themselves when they visit their doctor. Many have forgotten or are unaware of what vaccines adults should have – be they "booster" shots for certain diseases or recommended shots for seniors.
Some misconceptions about vaccines also continue to linger. Physicians often hear patients say that a flu shot will give them the flu (it won’t), that they had a flu shot last year so they don’t need one this year (you need one every year because the vaccine only lasts a year and changes annually due to different strains of flu), or that they were vaccinated for a disease when they were a child (some vaccines don’t provide lifelong immunity).

 A minority of people also believe that vaccines are unsafe and are a contributing factor in some diseases - they’re not.
Getting the vaccines is also a concern. Many physician offices, particularly smaller ones, find it impractical or too expensive to store vaccines for the needs of all their patients. Some vaccines have special storage requirements, all have expiration dates, and if they are stored too long or improperly (subject to excessive heat or cold, for example), they lose their effectiveness.
Finally, cost may be a factor for some, particularly for those on limited incomes. Insurance policies have different deductibles and different provisions on what is covered, and some shots can be expensive if one has to pay out of pocket.
Read more: 

México a la vanguardia en el Síndrome de Post Polio

Aug 23, 2012

Abrahão Augusto Juviniano Quadros post-poliomyelitis syndrome

Frequency and clinical manifestations of post-poliomyelitis syndrome in a brazilian tertiary care center

Frequência e manifestações clínicas da síndrome pós-poliomielite em um centro terciário brasileiro

Abrahão Augusto Juviniano QuadrosI; Mônica Tilli Reis Pessoa CondeII; Luis Fabiano MarinIII; Helga Cristina Almeida SilvaIII; Tatiana Mesquita e SilvaIII; Maria Bernadete Eduardo de PaulaIV; Roberto Dias Batista PereiraIII; Paulo Eduardo RamosIII; Gislane AbeIII; Acary Souza Bulle OliveiraIII
IDepartment of Neurology and Neurosurgery, Division of Neuromuscular Disorders, Federal University of São Paulo (Unifesp); Neurologic Rehabilitation Service of the Policlínica at Centro Universitário Adventista de São Paulo (Unasp), São Paulo SP, Brazil
IICenter for Disease Control and Prevention of the Municipal Secretary Office of Health, São Paulo SP, Brazil
IIIDepartment of Neurology and Neurosurgery, Division of Neuromuscular Disorders, Federal University of São Paulo (Unifesp), São Paulo SP, Brazil
IVCenter for Vigilance Epidemiology of the State Secretary Office of Health, São Paulo SP, Brazil


OBJECTIVE: To determine the frequency and clinical manifestations of patients with post-poliomyelitis syndrome (PPS) in a Brazilian division of neuromuscular disorders.
METHODS: A total of 167 patients with prior history of paralytic poliomyelitis was investigated for PPS, based on international diagnostic criteria. Other variables analyzed were: gender, race, age at poliomyelitis infection, age at PPS onset, and PPS symptoms.
RESULTS: One hundred and twenty-nine patients presented PPS, corresponding to 77.2% of the studied population. 62.8% were women and 37.2% were men. Mean age of patients with PPS at onset of PPS symptoms was 39.9±9.69 years. Their main clinical manifestations were: new weakness in the previously affected limbs (69%) and in the apparently not affected limbs (31%); joint pain (79.8%); fatigue (77.5%); muscle pain (76%); and cold intolerance (69.8%).
CONCLUSIONS: Most patients of our sample presented PPS. In Brazil, PPS frequency and clinical features are quite similar to those of other countries.
Key words: post-polio syndrome, poliomyelitis, prevalence.

México a la vanguardia en el Síndrome de Post Polio

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