What role do NADH and FADH2 play in the process of cellular respiration?

Answer 1

ATP has a high energy bond that can be broken to supply power to most of the cell.

NAD is a co-enzyme that is mainly absorbed from food or produced naturally in the body from certain nutritional elements, by means of various biochemical processes. Most niacin in food is in the form of NAD or NADP. Niacin is absorbed in the small intestine, mostly in the form of NAD or NADP. NAD is mainly obtained from the NAD that is present in food. NAD can be produced in the liver, in particular, under the control of the hormones that are secreted by the adrenal glands. Nicotinamide is an important precursor of NAD, under physiological conditions. Tryptophan is another important precursor of NAD and the body obtains a large proportion of NAD from this source. In the case of human nutrition, 60 mg tryptophan is the equivalent of 1 mg niacin.

BIOCHEMICAL FUNCTIONS OF NAD NAD was the first co-enzyme to be identified in 1905 by Harden and Young. NAD has more than 100 functions in the human metabolism. Even the activity of the citric-acid cycle, which is found in most cells, becomes restricted in the lack of NAD and NADP. The body constantly requires NAD and if the NAD level becomes too low, the need for it is activated in the primitive part of the brain. This biochemical action cannot be controlled by the mind or changed by willpower. Alcohol and the metabolites, which it creates, suppress this need for NAD. Excessive exercising and the associated secretion of endorphins also suppress the need for NAD. 1 Metabolic Detoxification of Chemical Substances NAD does not have the same side-effects as nicotinic acid at high dosages, like serious flushing and the release of histamine. The intracellular metabolism of alcohol, and possibly also of other chemical substances, requires NAD or derivatives thereof, in order to take place. Ninety per cent of alcohol is absorbed almost immediately in the body's cells; the remaining 10% is discharged mainly in the urine. Acetaldehyde is the first metabolite of various chemical substances, including alcohol, that is produced. Acetaldehyde is also formed during stress. Acetaldehyde is used as a preservative in certain dairy products. The last step in the metabolic detoxification process occurs in the citric-acid cycle, where three NADs are involved in the process. This cycle is also responsible for the conversion of proteins, carbohydrates and fats into ATP. This is a purely biochemical autonomic reaction, and neither the person's will or any other form of control can be exercised over it. The biochemical reactions can be simplified as follows: Chemical Substance + NAD -> Acetaldehyde + NAD -> Acetate + CoA -> Acetyl-CoA +3NAD(H) -> ATP + H2O + CO2 + Heat Ethanol toxicity is closely related to its metabolism in the liver. The elevated NADH/NAD ratio (ie NAD deficiency) results in alterations of the intermediary metabolism of lipids, carbohydrates, proteins, purines, hormones and porphyrins. This shift in metabolic pathways results in hyperlactacidaemia, lactacidosis, ketosis and hyperuricaemia. Furthermore, excess NADH can results in free radical production. The NADH that builds up, eg during eg alcohol metabolism, will drive pyruvate to lactate which can lead to acidosis. The pyruvate is now not available for gluconeogenesis and if, as is common in serious Alcoholism, the patient is not eating properly, hypoglycemia can result. The high NADH/NAD ratio will affect other processes such as b-oxidation. One clinical manifestation is liver disorders associated with alcoholism: fatty liver, alcoholic hepatitis and, sometimes, cirrhosis. The burden on oxidizing systems also leads to increased use of the P450 or microsomal oxidizing system which can have important effects on steroid metabolism and other processes involving this system. 2 Repairing DNA NAD and niacin (a precursor of NAD), play an important role in defending cells against DNA damage by genotoxic particles. Research shows that niacin supplementation, particularly for persons who initially have lower levels, improves the level of NAD in blood and lymphocytes. NAD plays a major role in repairing DNA. Research shows that damage to DNA can possibly stimulate the biosynthesis of NAD and that the repair of DNA can be increased and accelerated in cells with increased levels of NAD112. Cytotoxic substances reduce the intracellular levels of NAD and can lead to the death of cells. DNA strand breakage decreased proportionately to NAD concentrations over time in lymphocytes exposed to oxygen radicals. The results suggest a general correlation between DNA damage and acute lowering of cellular NAD pools. "Rejoining of DNA single-strand breaks generated by treatment of plasmids with gamma-rays, neocarzinostatin, or bleomycin was catalyzed inefficiently by human cell extracts. The reaction was strongly promoted by the addition of NAD+, which was employed for rapid and transient synthesis of poly(ADP-ribose)... NAD(+)-promoted DNA repair by soluble cell extracts also occurred with alkylated DNA as substrate and was suppressed by 3-aminobenzamide. A similar stimulatory effect by NAD+ was observed for repair of ultraviolet-irradiated DNA, and this could be ascribed to the presence of pyrimidine hydrates as minor radiation-induced DNA lesions". 3 Generating Energy During one of our dietitian's lectures in Nutritional Biochemistry at Pretoria University, an individual's theoretical daily need for NAD, assuming that none is recycled, was calculated. The calculation showed, that the average person's body contains approximately 16 grammes of NAD and that it had to be recycled 2 160 times during every 24 hours through the body. Had the body lacked the ability to recycle NAD successfully, 35,91 kg of NAD (approximately 72 000 containers of NutriNAD, or 7,2 million MultiNAD or MalaikaNAD capsules) would have to be taken every day, in order to supplement it. NAD plays an important role in the production of ATP (the basic energy molecule) in the body. NAD and NADP, which are pyridine nucleotides, are rated as being amongst the important high energy compounds in the biochemistry of organisms. The reduction of NAD plays an important part in the citric-acid cycle and contributes to the production of 22 molecules of ATP from one molecule of glucose. NAD and its derivatives NADH, NADP and NADPH have regulatory functions in the generation of triose phosphates and pyruvate from glucose. NAD is reduced to NADH in the metabolism of glucose. The hydrogen molecule is obtained from the metabolism of fats, carbohydrates and proteins. The activated NADH plays a part in several critical bodily functions, amongst others, in the continued production of ATP, which is the basic energy compound in the body. NAD plays an important role in the release of energy from carbohydrates, fats and proteins. In the absence of oxygen, pyruvate must be converted to lactate to regenerate NAD from NADH in the cytoplasm. In the presence of oxygen, the mitochondria can reoxidize cytosolic NADH by an indirect process, involving the mitochondrial "shuttle systems". 4 Improving Immunity Phagocytes use NADPH as a source of energy, to destroy pathogens. The NAD(P)H, that is available, is also used to protect the body against free radicals and to, in this way, prevent illnesses and damage. High dosages of ascorbic acid can supplement the activity of the NAD(P)H, which is only available to a limited extent. Research on the effect of the Epstein-Barr virus on lymphocytes, indicates that the cultivated cells' levels of NAD were lower. The addition of NAD restored the levels within two hours. The study also discusses the effect of NAD on the mitochondrial metabolism and the relationship between NAD and the activity of complex I in cultured human cells. .5 Improving Brain Functions The brain is metabolically speaking one of the most active organs in the body and consumes approximately 20% of all energy generated. Its weight-to-energy ratio is ten times more than that of most other organs. The brain does not really have any reserves of energy, in the true sense of the word, and must therefore be supplied continuously with energy by the body. The brain, as a whole, consumes approximately 4 x 1021 molecules of ATP per minute and this increases during REM sleeping. During the first ten years of a child's life, the brain consumes up to twice as much energy as during adulthood. When pyruvate oxidation is impaired, glycolysis will run faster than normal to try to make up for deficient ATP production. This will cause more production of lactate. The brain relies on oxidation of glucose as an energy source and has a limited ability to oxidize fatty acids. In cases of severe energy depletion mental retardation is not surprising. NAD plays an important part in the production of ATP in cells. Derivatives of niacin, mainly in the form of NAD and NADP coenzymes, are found abundantly in brain tissue. In the case of niacin deficiency, the brain's supply of NAD declines sharply and the functioning of the brain is disturbed; malfunctioning of the brain (dementia) is indeed one of the primary characteristics of pellagra. If the NAD deficiency lasts for an extended period, permanent brain damage develops. Scientists have discussed the possible use of NAD for the treatment of neurodegeneration155 and the improvement of brain functions. NADH plays a role in the synthesis of the neurotransmitters, i.e. noradrenaline and dopamine, which are important for maintaining a positive state of mind. South African research on NAD, that was conducted for the manufacturer, also confirms the normalising effect of NAD on the neurotransmitters, i.e. dopamine, adrenaline and noradrenaline. NAD probably plays a role in the production of serotonin and other neurotransmitters in the brain. 6 Normalizing Cell Functions "The corepressor CtBP (carboxyl-terminal binding protein) is involved in transcriptional pathways important for development, cell cycle regulation, and transformation. We demonstrate that CtBP binding to cellular and viral transcriptional repressors is regulated by the nicotinamide adenine dinucleotides NAD+ and NADH". "NAD is the substrate of a novel chromatin-associated enzyme-ADP-ribosyl transferase (ADPRT). In this study, the cell-cycle dependent change in cellular NAD content was observed in a line of human amnion FL cells. It was found that the cellular NAD content of FL cells was highest in G1 and lowest in S/G2-G2. 3AB, a potent ADPRT inhibitor, can inhibit the cell cycle dependent change in cellular NAD content and also inhibit DNA synthesis in the S phase and extend the S phase. The results indicate that ADP-ribosylation may be involved in DNA replication and cell cycle progression. It was also found that the DNA-damaging agents, MNNG, MMS and 4NQO could lower cellular NAD content in a dose-dependent way". "Hepatocytes were found to be remarkably resistant to suicidal NAD+ depletion due to consumption for chromatin-associated poly(ADP-ribose) biosynthesis, which normally follows infliction of DNA damage in mammalian cells... This differential behavior, demonstrable also with other carcinogens, can be attributed to the different NAD+ biosynthetic capacities of these cells".781 "Marked depletion of intracellular NAD+ prior to toxicity and a protection against toxicity associated with maintenance of NAD+ suggest a possible role for the maintenance of intracellular NAD+ in cellular integrity." "Many cellular enzymes use NAD+ as coenzyme or substrate, depending on the nature of the enzymatic reaction. Under certain conditions the cellular NAD+ concentration may become rate-limiting for such enzymes. For instance, when eucaryotic cells are exposed to high concentrations of DNA-damaging agents, the resulting DNA strand breaks may stimulate the nuclear enzyme poly(ADP-ribose) polymerase (PARP) to such an extent that the cellular pool of NAD+, which is the substrate for this enzyme, is severely depleted, possibly leading to acute cell death". "When mouse leukemia cells are treated with gamma-radiation or neocarzinostatin the intracellular NAD and ATP levels fall rapidly. We have shown that the ATP response is a consequence of the decreased NAD level. We suggest that this low NAD level results in decreased glycolytic activity and that there is a subsequent accumulation of phosphorylated sugars associated with the fall in ATP. Under these extreme conditions, therefore, the NAD level probably regulates the rate of glycolysis in cells which are utilising a rapidly metabolisable sugar as their energy source". "Ionizing- and ultraviolet-radiation cause cell damage or death by directly altering DNA and protein structures and by production of reactive oxygen species (ROS) and reactive carbonyl species (RCS). These processes disrupt cellular energy metabolism at multiple levels. The formation of DNA strand breaks activates signaling pathways that consume NAD, which can lead to the depletion of cellular ATP. Poly(ADP)-ribose polymerase (PARP-1) is the enzyme responsible for much of the NAD degradation following DNA damage, although numerous other PARPs have been discovered recently that await functional characterization. Studies on mouse epidermis in vivo and on human cells in culture have shown that UV-B radiation provokes the transient degradation of NAD and the synthesis of ADP-ribose polymers by PARP-1... Identifying approaches to optimize these responses while maintaining the energy status of cells is likely to be very important in minimizing the deleterious effects of solar radiation on skin". "Peroxynitrite and hydroxyl radicals are potent initiators of DNA single strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP-ribose)synthetase (PARS). Rapid activation of PARS depletes the intracellular concentration of its substrate, NAD+, slowing the rate of glycolysis, electron transport and ATP formation. This process can result in acute cell dysfunction and cell necrosis. Accordingly, inhibitors of PARS protect against cell death under these conditions. In addition to the direct cytotoxic pathway regulated by DNA injury and PARS activation, PARS also appears to modulate the course of inflammation by regulating the expression of a number of genes... In vivo data demonstrate that inhibition of PARS protects against various forms of inflammation, including zymosan or endotoxin induced multiple organ failure, Arthritis, allergic encephalomyelitis, and diabetic islet cell destruction". "Recent studies point to the naturally occurring molecules in expression of radiation damage and in protection. DNA repair was shown to be one of the parameters that can be modified to attain improved protection. The need for a natural compound that can enhance DNA repair in order to improve cellular protection focused our attention on nicotinamide (NA). The effects of addition of NA, a precursor for NAD+ synthesis, on the DNA repair capacity following gamma and ultraviolet irradiations were studied in several repair-proficient and repair-deficient cell lines. The addition of low concentrations of NA (less than 3 mM) resulted in increased repair synthesis in the repair-proficient cells. Addition to repair-deficient cells resulted in decreased repair synthesis. Cells which repair damage from one type of radiation, and not from another, responded accordingly to the presence of NA. However, addition of high concentrations of NA to repair-proficient cells resulted in decreased repair synthesis. Thus, nicotinamide can improve the repair capacity in a concentration-dependent manner, but it clearly requires the existence of functional repair processes." "An intimate relationship exists between DNA single-strand breaks, NAD metabolism, and cell viability in quiescent human lymphocytes. Under steady-state conditions, resting lymphocytes continually break and rejoin DNA. The balanced DNA excision-repair process is accompanied by a proportional consumption of NAD for poly(ADP-ribose) synthesis. However, lymphocytes have a limited capacity to resynthesize NAD from nicotinamide. An increase in DNA strand break formation in lymphocytes, or a block in DNA repair, accelerates poly(ADP-ribose) formation and may induce lethal NAD and ATP depletion". "These data indicate for the first time hormonal modulation of NADase resulting in two signals: (1) enhancement of NAD+ which may explain the increase in ADP ribosylation and activation of cholera-toxin substrates leading to facilitation of protein secretion; (2) suppression of cell cADP-ribose and consequently intracellular Ca2+ which may explain the melatonin-induced inhibition of protein secretion". "Extracellular NAD is degraded to pyridine and purine metabolites by different types of surface-located enzymes which are expressed differently on the plasmamembrane of various human cells and tissues... ATP was found to be the main labeled intracellular product of exogenous NAD catabolism; ADP, AMP, inosine and adenosine were also detected but in small quantities... These results confirm that adenosine is the NAD hydrolysis product incorporated by cells and further metabolized to ATP, and that adenosine transport is partially ATP dependent". Copyright article from the E-book NAD Therapy To Good Too Be True? Theo Verwey and Clinicians - see also http://www.nutrimalaika.net

Answer 2

these molecules can be thought of as "energy vouchers" They dont have any energy in them until they get to the electron transport chain. When they get there, the extra protons in these molecules are pumped against their concentration gradient (pumped from an area where there arent a lot of them to an area where there is a lot of them), and then the protons go through a turbine-like protein called ATP-Synthase, which produces ATP. So in short, FADH2 and NADH are used during the electron transport chain to produce the bulk of the ATP that cellular respiration yeilds.

Answer 3

they are used for energy to transport electrons through the electron transport chain

Answer 4

They store and transfer energy.