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Liver, Parkinson’s and Alzheimer’s Disease

Overt hepatic encephalopathy is generally taken to refer to a syndrome of neuropsychiatric, neuropsychological and neurological disturbances that may arise as a complication of liver disease, and which is reversible.2 This definition is not entirely consistent with the current state of knowledge, however, as there is growing evidence that the reversibility of the syndrome is not complete.11,,12

A recent consensus statement, published following the World Congress of Gastroenterology in 1998, suggested that hepatic encephalopathy be divided into three main types, with further subdivisions within one of the categories (Table 1).13

View this table:

  • Enlarge table
  •  Proposed nomenclature of hepatic encephalopathy (HE)13
  • Table 1
HE type Nomenclature Subcategory Subdivisions
A Encephalopathy associated with acute liver failure
B Encephalopathy associated with portal-systemic bypass, but no intrinsic hepatocellular disease
C Encephalopathy associated with Episodic HE Precipitated
    cirrhosis and portal hypertension or Persistent HE Spontaneous
    portal-systemic shunts Minimal HE Recurrent
Mild
Severe
Treatment-dependent

Between 10 and 50% of patients with cirrhosis and/or porto-caval shunts will experience an episode of overt hepatic encephalopathy at some time during their illness, with the prevalence varying across the spectrum of severity of the cirrhosis.14,,15 The true incidence and prevalence of overt hepatic encephalopathy in these patients is difficult to establish, because of the considerable heterogeneity in aetiology and disease severity. It is also difficult to diagnose the more subtle forms of hepatic encephalopathy such as stage 1 (Table 2) and minimal hepatic encephalopathy. The lack of a gold standard for assessing the presence of hepatic encephalopathy means that the incidence of these more minor forms is difficult to ascertain.13

View this table:

  • Enlarge table
  •  The clinical stages of hepatic encephalopathy2,20
  • Table 2
Stage Mental state
1 Mild confusion, euphoria or depression, decreased attention, mental slowing, untidiness, slurred speech, irritability, reversal of sleep pattern, possible asterixis.
2 Drowsiness, lethargy, gross mental slowing, obvious personality changes, inappropriate behaviour, intermittent disorientation, lack of sphincter control, obvious asterixis.
3 Somnolent but rousable, unable to perform mental tasks, persistent disorientation, amnesia, occasional attacks of rage, incoherent speech, pronounced confusion, asterixis probably absent.
4 Coma.

The factors that can precipitate overt hepatic encephalopathy are well recognized, and include an oral protein load, gastrointestinal bleeding, electrolyte imbalance, infection and deteriorating liver function.2,,16

It is unlikely that a single mechanism underlies the whole syndrome of hepatic encephalopathy in all its various forms; a multifactorial pathogenesis is much more likely.17–,20 Current thinking suggests that a combination of chronic low-grade glial oedema17 and potentiation of the effects of gamma amino butyric acid (GABA) on the central nervous system by ammonia may be responsible for many of the symptoms of hepatic encephalopathy.

GABA is the major inhibitory neurotransmitter in the human brain.19 Increased GABA-mediated neurotransmission is known to cause impaired consciousness and psychomotor dysfunction.19 In animal models of hepatic encephalopathy, an increase in GABA-ergic tone has been demonstrated due to both an increase in GABA release and enhanced activation of the GABA-A receptor complex.18 Benzodiazepines can act at the GABA-A receptor complex, and increased concentrations of endogenous benzodiazepines are found in the brain in liver failure.18,21,,22

Ammonia is known to be neurotoxic, but usually at much higher levels than those found in liver failure, and even then it does not produce a syndrome like that seen in hepatic encephalopathy; in fact, it tends to cause neuronal excitation.2,,19 However, at the lower concentrations seen in hepatic encephalopathy, ammonia potentiates the actions of GABA, possibly by enhancing ligand binding to the GABA-A receptor complex.19 It is probably for this reason that some patients with hepatic encephalopathy improve following administration of the GABA-A receptor antagonist flumazenil.20,,23

In addition there is some evidence for involvement of the glutamatergic system in hepatic encephalopathy. Glutamate is the major excitatory neurotransmitter in the human brain, and ammonia reduces its synthesis and down-regulates the glutamate receptor in vitro. This would result in reduced excitatory transmission in the brain.18 The dopaminergic, serotonergic and opioid neurotransmitter systems have also been implicated in the pathogenesis of hepatic encephalopathy, and it is likely that all of them and possibly others are involved in this complex syndrome.2,,18

In fulminant hepatic failure where hepatic encephalopathy develops within 8 weeks of the onset of liver disease,24 autopsy reveals brain oedema and astrocyte swelling.20 In patients with cirrhosis and portal-systemic shunts, the typical finding is the Alzheimer type II astrocyte, which is the pathological hallmark of hepatic encephalopathy.2,,20 They are found in many locations, including the cortex and the lenticular, lateral thalamic, dentate and red nuclei.24 In turn, these abnormal astrocytes have been shown to be produced by ammonia.25 These findings are similar to those in the acquired hepatocerebral degeneration syndrome.26–,29

Recent studies have also shown increased levels of manganese in the basal ganglia and to a lesser extent other areas of the brain,30–,32 but the relevance of these findings is undetermined.

Overt or symptomatic hepatic encephalopathy is traditionally graded into four stages (Table 2). The clinical picture is of a derangement of consciousness accompanied by decreased (or occasionally increased) psychomotor activity that if left untreated progresses through increasing drowsiness, stupor and coma.33 Sleep disturbance is one of the more common early signs and occurs in nearly 50% of cases.34

As the encephalopathy progresses along this path, signs of pyramidal tract dysfunction such as hypertonia, hyperreflexia and extensor plantar responses are common, eventually being replaced by hypotonia as coma develops.2 The familiar sign of asterixis is well described in hepatic encephalopathy, but unfortunately also occurs in other metabolic encephalopathies and is not therefore pathognomonic.20 One of the areas in which hepatic encephalopathy can differ from other metabolic encephalopathies is in the early stages when the psychomotor retardation that occurs can produce a striking Parkinsonian syndrome.2 In one study, these Parkinsonian features were shown to correlate with the degree of T1 hyperintensity seen in the basal ganglia on cerebral magnetic resonance imaging and the changes in choline/creatine ratios in the basal ganglia on cerebral magnetic resonance spectroscopy.35

Source:

http://qjmed.oxfordjournals.org/content/96/9/623

Connie’s Comments: Check for manganese or other metal toxicity that can harm the liver.

 

What are the most challenging memory-related situations for people with early stage Alzheimer’s?

What are the most challenging memory-related situations for people with early stage Alzheim… by Connie b. Dellobuono

Answer by Connie b. Dellobuono:

Memory loss varies in each person who are experiencing the early stage of Dementia that transforms into full blown Alzheimer's Disease. A senior was driving for 4hours because she does not know where and why she is driving. A friend could not recall new memories and walks slow and imbalance. A grandpa becomes distant and cannot sleep at night and later on became angry and aggressive. A 65yr old does not want to change her clothes or shower for a week and mumbles without any sense, this started when her partner died. There are many more stories of Alzheimer's disease but some are mild, they just sleep more and pets their stuff animal toys. Be with them always as they need to navigate the confusion in their brain but early stage is full of emotions.

What are the most challenging memory-related situations for people with early stage Alzheimer's?

Do Lifestyle or Social Factors Explain Ethnic/Racial Inequalities in Breast Cancer Survival?

Socio Economic position (SEP) explains more of the disparities for African-American versus white women in the United States compared with other ethnic comparisons. The role of SEP appears to be smaller in more recently published papers. We also found that the differences in breast cancer survival between ethnic groups may in part be explained by BMI, but there is little evidence to implicate smoking or alcohol consumption as explanatory factors for this inequality. Furthermore, given social patterning of BMI and other lifestyle habits, it is possible that our results for SEP and BMI are measuring the same effect.

A suggestion frequently made regarding ethnic inequalities in health is that there may be an underlying genetic basis for these inequalities. Although there is a lack of major systematic genetic differences between ethnic groups, there are extensive differences in lifestyle, suggesting that health disparities are most likely driven by environmental factors (1, 2). In relation to breast cancer survival, although differences in certain allele frequencies have been related to prognosis, we are not aware of any studies demonstrating that these differences could explain ethnic inequalities in survival. On the contrary, numerous studies point to equally plausible, and more coherent, alternative explanations for the observed inequalities. The majority of this evidence relates to Asian women. Comparisons within one ethnic group cannot be explained by differences in genetic makeup. Chuang et al. (69) found that Chinese women born in the United States had better survival than Chinese women born in East Asia (HR = 1.22, 95% CI: 1.06, 1.40). Similarly, changes in survival across generations among immigrant women are an indicator of the importance of environmental and cultural factors. Pineda et al. (70) demonstrated such changes for Chinese and Japanese, although not for Filipino, women. These variations were almost fully explained by demographic and stage- and treatment-related factors.

Some environmental exposures that are culturally related are likely to persist across generations. Furthermore, living as a first-generation immigrant in a country poses its own challenges, and linguistic and cultural barriers in access to care are likely to be important (69). The evidence above is supplemented by observations of changes over time in survival inequalities between ethnic groups. Jatoi et al. (71) documented widening inequality in all-cause mortality following breast cancer between black women and white women in the United States. This effect was driven by the most recently diagnosed cohort of women (1995–1999). Such changes are more plausibly explained by improvements in the health system being better tailored to a dominant ethnic group. Finally, the importance of SEP and BMI in explaining inequalities, as shown in this review, adds to the evidence that genetic differences between ethnic groups are unlikely to be important determinants of inequalities.

Evidence is accumulating that women of different ethnicities experience disproportionate risks of various breast cancer subtypes. For example, we have shown that, in New Zealand, Māori and Pacific women are more likely than non-Māori/non-Pacific women to have human epidermal growth factor receptor-2–positive breast cancer (72). Māori women are less likely and Pacific women more likely than non-Māori/non-Pacific women to have a negative estrogen receptor and progesterone receptor status. In the United States, Hispanic women are more likely to have estrogen receptor and progesterone receptor negative breast cancer compared with non-Hispanic white women (73), and black women are more likely than white women to have triple-negative breast cancer (74). When Chinese women were compared with white American women, no differences in estrogen receptor or progesterone receptor status were found (69). Because receptor-negative breast cancer is not amenable to hormonal therapy, these ethnic differences could explain some of the inequalities in survival. However, even among women with triple-negative breast cancer, 5-year relative survival was lowest in the non-Hispanic black group (74). The presence of differential subtypes of disease could be due to differential risk factors, and breast cancer epidemiologists should refine their outcomes to account for these differences.

Our final analysis showed that adjusting the breast cancer survival inequalities for measures of SEP had a greater impact in studies of African-American versus white women compared with other ethnic comparisons. This finding is partly due to the higher crude inequality in survival between African-American and white women (Figure 3A), so there was more inequality to “explain” through adjustment. However, it is probably also partly due to the higher proportion of African Americans (compared with other ethnic minorities) living in poverty (25% vs. 8%) (75) and the probable higher level of resulting socioeconomic homogeneity in the census groups used to assign SEP in the studies included in this review. The effect of adjusting ethnic inequalities in health for SEP is strongly affected by the choice of SEP measure, and health inequalities between different ethnic groups respond in different ways to this adjustment (76). Therefore, the aggregation of different ethnic groups, as seen in several of the included studies (e.g., the grouping “Asian/Pacific Islander” in the United States and “South Asian” in the United Kingdom) could be masking the real effect that various individual-level measures of SEP would have on ethnic inequalities in survival.

One final study, which followed up women diagnosed with breast cancer in the Women’s Health Initiative, found that after adjusting for age, stage of disease, BMI, and whether the women was in the clinical or observational arm of the study, a significant increased risk of death still remained for African-American compared with white women (50).

Five studies (9 comparisons) contributed to the overall crude analyses. The pooled hazard ratio showed that women in the minority ethnic groups were more likely to die during follow-up (HR = 1.38, 95% CI: 1.16, 1.64) (Figure 3A). However, there was significant heterogeneity between studies (P < 0.001).

Correspondence to Fiona McKenzie, Centre for Public Health Research, Massey University, Private Bag 756, Wellington, New Zealand (e-mail: f.j.mckenzie@massey.ac.nz).

Source:

http://epirev.oxfordjournals.org/content/31/1/52.full?sid=2aab17bb-27b8-4a3e-b7ae-2895120a53da#sec-7

 

US Obesity epidemic

geo epi.JPGchildren obese epiobesity epi gender and ageobesity epi p2obesity epi p1

socio eco epiIncrease in Portion Sizes in the United States

A study compared current portions of food products in the United States with past portions, concluding that the sizes of current marketplace foods almost universally exceed those offered in the past. The trend toward larger portion sizes in the United States began in the 1970s, and portion sizes increased sharply in the 1980s and have continued to increase. Study results show that, except for sliced white bread, all of the commonly available food portions exceeded the US Department of Agriculture and Food and Drug Administration standard portions, sometimes to a great extent. For example, the largest excess over US Department of Agriculture standards by 700 percent occurred in the cookie category, while cooked pasta, muffins, steaks, and bagels exceeded standards by 480 percent, 333 percent, 224 percent, and 195 percent, respectively. For french fries, hamburgers, and soda, the current portion sizes are 2–5 times larger than in the past (78). The influence of growing portion size on people’s energy intake is magnified by the fact that more people in the United States increasingly eat meals away from home more often than they did in the past (73).

Dietary intake data collected from individuals also support a marked trend toward larger portion sizes in the United States. Based on nationally representative data collected between 1977 and 1996, a study reported that the portion sizes of food consumed both at home and outside the home had increased for a large number of foods. Some of the increases were substantial, very often ranging between 50 kcal and 150 kcal per item for commonly consumed food items such as salty snacks, soft drinks, hamburgers, french fries, and Mexican food. The potential impact of larger portion sizes on people’s overconsumption of energy and weight gain can be remarkable. For example, an added 10 kcal per day of extra calories can result in an extra pound (0.45 kg) of weight gained per year (75).

Source:

Epidemiologic Reviews by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

http://epirev.oxfordjournals.org/content/29/1/6.full#app-3

 

 

Garden at hiddenvilla.org for Alzheimer’s

alz garden

Our schedule to volunteer and garden at hiddenvilla.org in Los Altos is on:

Wednesday, July 13
Wednesday, August 17
Wednesday, August 24
Wednesday, September 28
Hidden Villa’s CSA program manages the organic farming operations, including harvesting, planting, scheduling, distribution, and the relationships with the CSA subscribers and the Community Services Agency of Mountain View. The CSA donates over 44,000 servings of organic produce annually to the local food bank which supports over 3,000 local families.

Care for your parents

Elder abuse day.JPG

Today is Elder Abuse Day. Visit, talk and care for your mom and dad. Many seniors in care homes are seldom visited by their love ones. It brings a smile in their face and gives them good sleep when visited by their love ones.

Many of their anxiety can be resolved by a calm and loving voice from their children or grandchildren. It is not late to care for them. You will be blessed.

Email Connie at motherhealth@gmail.com if you need a caregiver in the bayarea and any suggestions for a new mobile app to connect older adults to caregivers and their doctors.  Mobile app developers are needed to give your input (tips and suggestions) in a new mobile app for coordinated and integrated care for families, nursing homes and hospitals.

I regularly visit a care home in San Jose and dance in front of seniors to make them laugh and be happy (see senior in wheel chair laughing and watching me dance).

cropped-logo.jpg

Build your network and fund your dream

build your network and fund your dream.JPGA start-up crowd funding, smashfund.com , will launch this July. Before then, it is free to join now by clicking the image above in Chrome not Explorer.  You join because you will be sharing in the company’s profit (derived from membership fee – $150 – which will start after launch) for every person you invited now.
100% of the crowd-funded money goes to the crowd-funder (person,non-profit,etc).

Email support@smashfund.com for more info after you join FREE now.  You will get a link to share with others to get paid later after launch.

 

NAD , metabolic aging and Alzheimer and Parkinson

CD38 NAD NADH metabolic agingNAD and ADNAD usesNAD and agingNAD and redox resveratrol and agingNAD - less as we age - metabolism and agingReferences

  1. ^ Jump up to: a b c Pollak N, Dölle C, Ziegler M (2007). “The power to reduce: pyridine nucleotides – small molecules with a multitude of functions”. Biochem. J. 402 (2): 205–18. doi:10.1042/BJ20061638. PMC 1798440. PMID 17295611. 
  2. ^ Jump up to: a b c d e f Belenky P, Bogan KL, Brenner C (2007). “NAD+ metabolism in health and disease” (PDF). Trends Biochem. Sci. 32 (1): 12–9. doi:10.1016/j.tibs.2006.11.006. PMID 17161604. Retrieved 2007-12-23. 
  3. Jump up ^ Unden G, Bongaerts J (1997). “Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors”. Biochim. Biophys. Acta 1320 (3): 217–34. doi:10.1016/S0005-2728(97)00034-0. PMID 9230919. 
  4. Jump up ^ Windholz, Martha (1983). The Merck Index: an encyclopedia of chemicals, drugs, and biologicals (10th ed.). Rahway NJ, US: Merck. p. 909. ISBN 0-911910-27-1. 
  5. Jump up ^ Biellmann JF, Lapinte C, Haid E, Weimann G (1979). “Structure of lactate dehydrogenase inhibitor generated from coenzyme”. Biochemistry 18 (7): 1212–7. doi:10.1021/bi00574a015. PMID 218616. 
  6. ^ Jump up to: a b Dawson, R. Ben (1985). Data for biochemical research (3rd ed.). Oxford: Clarendon Press. p. 122. ISBN 0-19-855358-7. 
  7. ^ Jump up to: a b Lakowicz JR, Szmacinski H, Nowaczyk K, Johnson ML (1992). “Fluorescence lifetime imaging of free and protein-bound NADH”. Proc. Natl. Acad. Sci. U.S.A. 89 (4): 1271–5. Bibcode:1992PNAS…89.1271L. doi:10.1073/pnas.89.4.1271. PMC 48431. PMID 1741380. 
  8. Jump up ^ Jameson DM, Thomas V, Zhou DM (1989). “Time-resolved fluorescence studies on NADH bound to mitochondrial malate dehydrogenase”. Biochim. Biophys. Acta 994 (2): 187–90. doi:10.1016/0167-4838(89)90159-3. PMID 2910350. 
  9. Jump up ^ Kasimova MR, Grigiene J, Krab K, Hagedorn PH, Flyvbjerg H, Andersen PE, Møller IM (2006). “The Free NADH Concentration Is Kept Constant in Plant Mitochondria under Different Metabolic Conditions”. Plant Cell 18 (3): 688–98. doi:10.1105/tpc.105.039354. PMC 1383643. PMID 16461578. 
  10. Jump up ^ Reiss PD, Zuurendonk PF, Veech RL (1984). “Measurement of tissue purine, pyrimidine, and other nucleotides by radial compression high-performance liquid chromatography”. Anal. Biochem. 140 (1): 162–71. doi:10.1016/0003-2697(84)90148-9. PMID 6486402. 
  11. Jump up ^ Yamada K, Hara N, Shibata T, Osago H, Tsuchiya M (2006). “The simultaneous measurement of nicotinamide adenine dinucleotide and related compounds by liquid chromatography/electrospray ionization tandem mass spectrometry”. Anal. Biochem. 352 (2): 282–5. doi:10.1016/j.ab.2006.02.017. PMID 16574057. 
  12. ^ Jump up to: a b Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, Lamming DW, Souza-Pinto NC, Bohr VA, Rosenzweig A, de Cabo R, Sauve AA, Sinclair DA (2007). “Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival”. Cell 130 (6): 1095–107. doi:10.1016/j.cell.2007.07.035. PMC 3366687. PMID 17889652. 
  13. Jump up ^ Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, Brenner C (2007). “Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+“. Cell 129 (3): 473–84. doi:10.1016/j.cell.2007.03.024. PMID 17482543. 
  14. Jump up ^ Blinova K, Carroll S, Bose S, Smirnov AV, Harvey JJ, Knutson JR, Balaban RS (2005). “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions”. Biochemistry 44 (7): 2585–94. doi:10.1021/bi0485124. PMID 15709771. 
  15. Jump up ^ Todisco S, Agrimi G, Castegna A, Palmieri F (2006). “Identification of the mitochondrial NAD+ transporter in Saccharomyces cerevisiae“. J. Biol. Chem. 281 (3): 1524–31. doi:10.1074/jbc.M510425200. PMID 16291748. 
  16. Jump up ^ Schafer FQ, Buettner GR (2001). “Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple”. Free Radic Biol Med 30 (11): 1191–212. doi:10.1016/S0891-5849(01)00480-4. PMID 11368918. 
  17. Jump up ^ Williamson DH, Lund P, Krebs HA (1967). “The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver”. Biochem. J. 103 (2): 514–27. PMC 1270436. PMID 4291787. 
  18. Jump up ^ Zhang Q, Piston DW, Goodman RH (2002). “Regulation of corepressor function by nuclear NADH”. Science 295 (5561): 1895–7. doi:10.1126/science.1069300. PMID 11847309. 
  19. Jump up ^ Lin SJ, Guarente L (April 2003). “Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease”. Curr. Opin. Cell Biol. 15 (2): 241–6. doi:10.1016/S0955-0674(03)00006-1. PMID 12648681. 
  20. Jump up ^ Veech RL, Eggleston LV, Krebs HA (1969). “The redox state of free nicotinamide–adenine dinucleotide phosphate in the cytoplasm of rat liver”. Biochem. J. 115 (4): 609–19. PMC 1185185. PMID 4391039. 
  21. Jump up ^ Katoh A, Uenohara K, Akita M, Hashimoto T (2006). “Early Steps in the Biosynthesis of NAD in Arabidopsis Start with Aspartate and Occur in the Plastid”. Plant Physiol. 141 (3): 851–7. doi:10.1104/pp.106.081091. PMC 1489895. PMID 16698895. 
  22. Jump up ^ Foster JW, Moat AG (1 March 1980). “Nicotinamide adenine dinucleotide biosynthesis and pyridine nucleotide cycle metabolism in microbial systems”. Microbiol. Rev. 44 (1): 83–105. PMC 373235. PMID 6997723. 
  23. Jump up ^ Magni G, Orsomando G, Raffaelli N (2006). “Structural and functional properties of NAD kinase, a key enzyme in NADP biosynthesis”. Mini reviews in medicinal chemistry 6 (7): 739–46. doi:10.2174/138955706777698688. PMID 16842123. 
  24. Jump up ^ Sakuraba H, Kawakami R, Ohshima T (2005). “First Archaeal Inorganic Polyphosphate/ATP-Dependent NAD Kinase, from Hyperthermophilic Archaeon Pyrococcus horikoshii: Cloning, Expression, and Characterization”. Appl. Environ. Microbiol. 71 (8): 4352–8. doi:10.1128/AEM.71.8.4352-4358.2005. PMC 1183369. PMID 16085824. 
  25. Jump up ^ Raffaelli N, Finaurini L, Mazzola F, Pucci L, Sorci L, Amici A, Magni G (2004). “Characterization of Mycobacterium tuberculosis NAD kinase: functional analysis of the full-length enzyme by site-directed mutagenesis”. Biochemistry 43 (23): 7610–7. doi:10.1021/bi049650w. PMID 15182203. 
  26. Jump up ^ Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H, Lin SS, Manchester JK, Gordon JI, Sinclair DA (2002). “Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels”. J. Biol. Chem. 277 (21): 18881–90. doi:10.1074/jbc.M111773200. PMID 11884393. 
  27. Jump up ^ Billington RA, Travelli C, Ercolano E, Galli U, Roman CB, Grolla AA, Canonico PL, Condorelli F, Genazzani AA (2008). “Characterization of NAD Uptake in Mammalian Cells”. J. Biol. Chem. 283 (10): 6367–74. doi:10.1074/jbc.M706204200. PMID 18180302. 
  28. Jump up ^ Henderson LM (1983). “Niacin”. Annu. Rev. Nutr. 3: 289–307. doi:10.1146/annurev.nu.03.070183.001445. PMID 6357238. 
  29. ^ Jump up to: a b Rongvaux A, Andris F, Van Gool F, Leo O (2003). “Reconstructing eukaryotic NAD metabolism”. BioEssays 25 (7): 683–90. doi:10.1002/bies.10297. PMID 12815723. 
  30. Jump up ^ Ma B, Pan SJ, Zupancic ML, Cormack BP (2007). “Assimilation of NAD+ precursors in Candida glabrata“. Mol. Microbiol. 66 (1): 14–25. doi:10.1111/j.1365-2958.2007.05886.x. PMID 17725566. 
  31. Jump up ^ Reidl J, Schlör S, Kraiss A, Schmidt-Brauns J, Kemmer G, Soleva E (2000). “NADP and NAD utilization in Haemophilus influenzae“. Mol. Microbiol. 35 (6): 1573–81. doi:10.1046/j.1365-2958.2000.01829.x. PMID 10760156. 
  32. Jump up ^ Gerdes SY, Scholle MD, D’Souza M, Bernal A, Baev MV, Farrell M, Kurnasov OV, Daugherty MD, Mseeh F, Polanuyer BM, Campbell JW, Anantha S, Shatalin KY, Chowdhury SA, Fonstein MY, Osterman AL (2002). “From Genetic Footprinting to Antimicrobial Drug Targets: Examples in Cofactor Biosynthetic Pathways”. J. Bacteriol. 184 (16): 4555–72. doi:10.1128/JB.184.16.4555-4572.2002. PMC 135229. PMID 12142426. 
  33. Jump up ^ Senkovich O, Speed H, Grigorian A, et al. (2005). “Crystallization of three key glycolytic enzymes of the opportunistic pathogen Cryptosporidium parvum“. Biochim. Biophys. Acta 1750 (2): 166–72. doi:10.1016/j.bbapap.2005.04.009. PMID 15953771. 
  34. ^ Jump up to: a b c Smyth LM, Bobalova J, Mendoza MG, Lew C, Mutafova-Yambolieva VN (2004). “Release of beta-nicotinamide adenine dinucleotide upon stimulation of postganglionic nerve terminals in blood vessels and urinary bladder”. J Biol Chem. 279 (47): 48893–903. doi:10.1074/jbc.M407266200. PMID 15364945. 
  35. ^ Jump up to: a b c Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M, Zocchi E (2006). “Emerging functions of extracellular pyridine nucleotides”. Mol Med. 12 (11–12): 324–7. doi:10.2119/2006-00075.Billington. PMC 1829198. PMID 17380199. 
  36. Jump up ^ “Enzyme Nomenclature, Recommendations for enzyme names from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology”. Retrieved 2007-12-06. 
  37. Jump up ^ “NiceZyme View of ENZYME: EC 1.6.5.3”. Expasy. Retrieved 2007-12-16. 
  38. Jump up ^ Lesk AM (1995). “NAD-binding domains of dehydrogenases”. Curr. Opin. Struct. Biol. 5 (6): 775–83. doi:10.1016/0959-440X(95)80010-7. PMID 8749365. 
  39. ^ Jump up to: a b Rao ST, Rossmann MG (1973). “Comparison of super-secondary structures in proteins”. J Mol Biol 76 (2): 241–56. doi:10.1016/0022-2836(73)90388-4. PMID 4737475. 
  40. Jump up ^ Goto M, Muramatsu H, Mihara H, Kurihara T, Esaki N, Omi R, Miyahara I, Hirotsu K (2005). “Crystal structures of Delta1-piperideine-2-carboxylate/Delta1-pyrroline-2-carboxylate reductase belonging to a new family of NAD(P)H-dependent oxidoreductases: conformational change, substrate recognition, and stereochemistry of the reaction”. J. Biol. Chem. 280 (49): 40875–84. doi:10.1074/jbc.M507399200. PMID 16192274. 
  41. ^ Jump up to: a b Bellamacina CR (1 September 1996). “The nicotinamide dinucleotide binding motif: a comparison of nucleotide binding proteins”. FASEB J. 10 (11): 1257–69. PMID 8836039. 
  42. Jump up ^ Carugo O, Argos P (1997). “NADP-dependent enzymes. I: Conserved stereochemistry of cofactor binding”. Proteins 28 (1): 10–28. doi:10.1002/(SICI)1097-0134(199705)28:1<10::AID-PROT2>3.0.CO;2-N. PMID 9144787. 
  43. Jump up ^ Vickers TJ, Orsomando G, de la Garza RD, Scott DA, Kang SO, Hanson AD, Beverley SM (2006). “Biochemical and genetic analysis of methylenetetrahydrofolate reductase in Leishmania metabolism and virulence”. J. Biol. Chem. 281 (50): 38150–8. doi:10.1074/jbc.M608387200. PMID 17032644. 
  44. Jump up ^ Bakker BM, Overkamp KM, Kötter P, Luttik MA, Pronk JT (2001). “Stoichiometry and compartmentation of NADH metabolism in Saccharomyces cerevisiae“. FEMS Microbiol. Rev. 25 (1): 15–37. doi:10.1111/j.1574-6976.2001.tb00570.x. PMID 11152939. 
  45. Jump up ^ Rich PR (2003). “The molecular machinery of Keilin’s respiratory chain”. Biochem. Soc. Trans. 31 (Pt 6): 1095–105. doi:10.1042/BST0311095. PMID 14641005. 
  46. Jump up ^ Heineke D, Riens B, Grosse H, Hoferichter P, Peter U, Flügge UI, Heldt HW (1991). “Redox Transfer across the Inner Chloroplast Envelope Membrane”. Plant Physiol 95 (4): 1131–1137. doi:10.1104/pp.95.4.1131. PMC 1077662. PMID 16668101. 
  47. ^ Jump up to: a b Nicholls DG; Ferguson SJ (2002). Bioenergetics 3 (1st ed.). Academic Press. ISBN 0-12-518121-3. 
  48. Jump up ^ Sistare FD, Haynes RC (15 October 1985). “The interaction between the cytosolic pyridine nucleotide redox potential and gluconeogenesis from lactate/pyruvate in isolated rat hepatocytes. Implications for investigations of hormone action”. J. Biol. Chem. 260 (23): 12748–53. PMID 4044607. 
  49. Jump up ^ Freitag A, Bock E (1990). “Energy conservation in Nitrobacter“. FEMS Microbiology Letters 66 (1–3): 157–62. doi:10.1111/j.1574-6968.1990.tb03989.x. 
  50. Jump up ^ Starkenburg SR, Chain PS, Sayavedra-Soto LA, Hauser L, Land ML, Larimer FW, Malfatti SA, Klotz MG, Bottomley PJ, Arp DJ, Hickey WJ (2006). “Genome Sequence of the Chemolithoautotrophic Nitrite-Oxidizing Bacterium Nitrobacter winogradskyi Nb-255″. Appl. Environ. Microbiol. 72 (3): 2050–63. doi:10.1128/AEM.72.3.2050-2063.2006. PMC 1393235. PMID 16517654. 
  51. Jump up ^ Ziegler M (2000). “New functions of a long-known molecule. Emerging roles of NAD in cellular signaling”. Eur. J. Biochem. 267 (6): 1550–64. doi:10.1046/j.1432-1327.2000.01187.x. PMID 10712584. 
  52. ^ Jump up to: a b Diefenbach J, Bürkle A (2005). “Introduction to poly(ADP-ribose) metabolism”. Cell. Mol. Life Sci. 62 (7–8): 721–30. doi:10.1007/s00018-004-4503-3. PMID 15868397. 
  53. Jump up ^ Berger F, Ramírez-Hernández MH, Ziegler M (2004). “The new life of a centenarian: signaling functions of NAD(P)”. Trends Biochem. Sci. 29 (3): 111–8. doi:10.1016/j.tibs.2004.01.007. PMID 15003268. 
  54. Jump up ^ Corda D, Di Girolamo M (2003). “New Embo Member’s Review: Functional aspects of protein mono-ADP-ribosylation”. EMBO J. 22 (9): 1953–8. doi:10.1093/emboj/cdg209. PMC 156081. PMID 12727863. 
  55. ^ Jump up to: a b Bürkle A (2005). “Poly(ADP-ribose). The most elaborate metabolite of NAD+“. FEBS J. 272 (18): 4576–89. doi:10.1111/j.1742-4658.2005.04864.x. PMID 16156780. 
  56. Jump up ^ Seman M, Adriouch S, Haag F, Koch-Nolte F (2004). “Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling”. Curr. Med. Chem. 11 (7): 857–72. doi:10.2174/0929867043455611. PMID 15078170. 
  57. Jump up ^ Chen YG, Kowtoniuk WE, Agarwal I, Shen Y, Liu DR (December 2009). “LC/MS analysis of cellular RNA reveals NAD-linked RNA”. Nat Chem Biol 5 (12): 879–881. doi:10.1038/nchembio.235. PMC 2842606. PMID 19820715. 
  58. Jump up ^ Guse AH (2004). “Biochemistry, biology, and pharmacology of cyclic adenosine diphosphoribose (cADPR)”. Curr. Med. Chem. 11 (7): 847–55. doi:10.2174/0929867043455602. PMID 15078169. 
  59. Jump up ^ Guse AH (2004). “Regulation of calcium signaling by the second messenger cyclic adenosine diphosphoribose (cADPR)”. Curr. Mol. Med. 4 (3): 239–48. doi:10.2174/1566524043360771. PMID 15101682. 
  60. Jump up ^ Guse AH (2005). “Second messenger function and the structure-activity relationship of cyclic adenosine diphosphoribose (cADPR)”. FEBS J. 272 (18): 4590–7. doi:10.1111/j.1742-4658.2005.04863.x. PMID 16156781. 
  61. Jump up ^ North BJ, Verdin E (2004). “Sirtuins: Sir2-related NAD-dependent protein deacetylases”. Genome Biol 5 (5): 224. doi:10.1186/gb-2004-5-5-224. PMC 416462. PMID 15128440. 
  62. Jump up ^ Blander G, Guarente L (2004). “The Sir2 family of protein deacetylases”. Annu. Rev. Biochem. 73: 417–35. doi:10.1146/annurev.biochem.73.011303.073651. PMID 15189148. 
  63. Jump up ^ Trapp J, Jung M (2006). “The role of NAD+ dependent histone deacetylases (sirtuins) in ageing”. Curr Drug Targets 7 (11): 1553–60. doi:10.2174/1389450110607011553. PMID 17100594. 
  64. Jump up ^ Wilkinson A, Day J, Bowater R (2001). “Bacterial DNA ligases”. Mol. Microbiol. 40 (6): 1241–8. doi:10.1046/j.1365-2958.2001.02479.x. PMID 11442824. 
  65. Jump up ^ Schär P, Herrmann G, Daly G, Lindahl T (1997). “A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks”. Genes & Development 11 (15): 1912–24. doi:10.1101/gad.11.15.1912. PMC 316416. PMID 9271115. 
  66. Jump up ^ Ziegler M, Niere M (2004). “NAD+ surfaces again”. Biochem. J. 382 (Pt 3): e5–6. doi:10.1042/BJ20041217. PMC 1133982. PMID 15352307. 
  67. Jump up ^ Koch-Nolte F, Fischer S, Haag F, Ziegler M (2011). “Compartmentation of NAD+-dependent signalling”. FEBS Lett. 585 (11): 1651–6. doi:10.1016/j.febslet.2011.03.045. PMID 21443875. 
  68. Jump up ^ Breen LT, Smyth LM, Yamboliev IA, Mutafova-Yambolieva VN (2006). “beta-NAD is a novel nucleotide released on stimulation of nerve terminals in human urinary bladder detrusor muscle”. Am. J. Physiol. Renal Physiol. 290 (2): F486–95. doi:10.1152/ajprenal.00314.2005. PMID 16189287. 
  69. ^ Jump up to: a b Mutafova-Yambolieva VN, Hwang SJ, Hao X, Chen H, Zhu MX, Wood JD, Ward SM, Sanders KM (2007). “Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle”. Proc. Natl. Acad. Sci. U.S.A. 104 (41): 16359–64. doi:10.1073/pnas.0705510104. PMC 2042211. PMID 17913880. 
  70. ^ Jump up to: a b Hwang SJ, Durnin L, Dwyer L, Rhee PL, Ward SM, Koh SD, Sanders KM, Mutafova-Yambolieva VN (2011). “β-nicotinamide adenine dinucleotide is an enteric inhibitory neurotransmitter in human and nonhuman primate colons”. Gastroenterology 140 (2): 608–617.e6. doi:10.1053/j.gastro.2010.09.039. PMC 3031738. PMID 20875415. 
  71. Jump up ^ Yamboliev IA, Smyth LM, Durnin L, Dai Y, Mutafova-Yambolieva VN (2009). “Storage and secretion of beta-NAD, ATP and dopamine in NGF-differentiated rat pheochromocytoma PC12 cells”. Eur. J. Neurosci. 30 (5): 756–68. doi:10.1111/j.1460-9568.2009.06869.x. PMC 2774892. PMID 19712094. 
  72. Jump up ^ Durnin L, Dai Y, Aiba I, Shuttleworth CW, Yamboliev IA, Mutafova-Yambolieva VN (2012). “Release, neuronal effects and removal of extracellular β-nicotinamide adenine dinucleotide (β-NAD+) in the rat brain”. Eur. J. Neurosci. 35 (3): 423–35. doi:10.1111/j.1460-9568.2011.07957.x. PMC 3270379. PMID 22276961. 
  73. Jump up ^ Sauve AA (March 2008). “NAD+ and vitamin B3: from metabolism to therapies”. The Journal of Pharmacology and Experimental Therapeutics 324 (3): 883–93. doi:10.1124/jpet.107.120758. PMID 18165311. 
  74. Jump up ^ Khan JA, Forouhar F, Tao X, Tong L (2007). “Nicotinamide adenine dinucleotide metabolism as an attractive target for drug discovery”. Expert Opin. Ther. Targets 11 (5): 695–705. doi:10.1517/14728222.11.5.695. PMID 17465726. 
  75. Jump up ^ Kaneko S, Wang J, Kaneko M, Yiu G, Hurrell JM, Chitnis T, Khoury SJ, He Z (2006). “Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models”. J. Neurosci. 26 (38): 9794–804. doi:10.1523/JNEUROSCI.2116-06.2006. PMID 16988050. 
  76. Jump up ^ Swerdlow RH (1998). “Is NADH effective in the treatment of Parkinson’s disease?”. Drugs Aging 13 (4): 263–8. doi:10.2165/00002512-199813040-00002. PMID 9805207. 
  77. Jump up ^ Timmins GS, Deretic V (2006). “Mechanisms of action of isoniazid”. Mol. Microbiol. 62 (5): 1220–7. doi:10.1111/j.1365-2958.2006.05467.x. PMID 17074073. 
  78. Jump up ^ Rawat R, Whitty A, Tonge PJ (2003). “The isoniazid-NAD adduct is a slow, tight-binding inhibitor of InhA, the Mycobacterium tuberculosis enoyl reductase: Adduct affinity and drug resistance”. Proc. Natl. Acad. Sci. U.S.A. 100 (24): 13881–6. Bibcode:2003PNAS..10013881R. doi:10.1073/pnas.2235848100. PMC 283515. PMID 14623976. 
  79. Jump up ^ Argyrou A, Vetting MW, Aladegbami B, Blanchard JS (2006). “Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid”. Nat. Struct. Mol. Biol. 13 (5): 408–13. doi:10.1038/nsmb1089. PMID 16648861. 
  80. Jump up ^ Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA (December 19, 2013). “Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging”. Cell 155 (7): 1624–1638. doi:10.1016/j.cell.2013.11.037. PMID 24360282. 
  81. ^ Jump up to: a b Pankiewicz KW, Patterson SE, Black PL, Jayaram HN, Risal D, Goldstein BM, Stuyver LJ, Schinazi RF (2004). “Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)—the major therapeutic target”. Curr. Med. Chem. 11 (7): 887–900. doi:10.2174/0929867043455648. PMID 15083807. 
  82. Jump up ^ Franchetti P, Grifantini M (1999). “Nucleoside and non-nucleoside IMP dehydrogenase inhibitors as antitumor and antiviral agents”. Curr. Med. Chem. 6 (7): 599–614. PMID 10390603. 
  83. Jump up ^ Kim EJ, Um SJ (2008). “SIRT1: roles in aging and cancer”. BMB Rep 41 (11): 751–6. doi:10.5483/BMBRep.2008.41.11.751. PMID 19017485. 
  84. Jump up ^ Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A (2006). “Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate”. Curr. Biol. 16 (3): 296–300. doi:10.1016/j.cub.2005.12.038. PMID 16461283. 
  85. Jump up ^ Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003). “Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan”. Nature 425 (6954): 191–6. Bibcode:2003Natur.425..191H. doi:10.1038/nature01960. PMID 12939617. 
  86. Jump up ^ Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004). “Sirtuin activators mimic caloric restriction and delay ageing in metazoans”. Nature 430 (7000): 686–9. Bibcode:2004Natur.430..686W. doi:10.1038/nature02789. PMID 15254550. 
  87. Jump up ^ Rizzi M, Schindelin H (2002). “Structural biology of enzymes involved in NAD and molybdenum cofactor biosynthesis”. Curr. Opin. Struct. Biol. 12 (6): 709–20. doi:10.1016/S0959-440X(02)00385-8. PMID 12504674. 
  88. Jump up ^ Begley TP, Kinsland C, Mehl RA, Osterman A, Dorrestein P (2001). “The biosynthesis of nicotinamide adenine dinucleotides in bacteria”. Vitam. Horm. Vitamins & Hormones 61: 103–19. doi:10.1016/S0083-6729(01)61003-3. ISBN 978-0-12-709861-6. PMID 11153263. 
  89. Jump up ^ http://www.cdc.gov/meningitis/lab-manual/chpt09-id-characterization-hi.html
  90. Jump up ^ Harden, A; Young, WJ (24 October 1906). “The alcoholic ferment of yeast-juice Part II.–The coferment of yeast-juice”. Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character 78 (526): 369–375. doi:10.1098/rspb.1906.0070. JSTOR 80144. 
  91. Jump up ^ “Fermentation of sugars and fermentative enzymes” (PDF). Nobel Lecture, 23 May 1930. Nobel Foundation. Retrieved 2007-09-30. 
  92. Jump up ^ Warburg O, Christian W (1936). “Pyridin, der wasserstoffübertragende bestandteil von gärungsfermenten (pyridin-nucleotide)” [Pyridin, the hydrogen-transferring component of the fermentation enzymes (pyridine nucleotide)]. Biochemische Zeitschrift (in German) 287: 291. doi:10.1002/hlca.193601901199. 
  93. Jump up ^ Elvehjem CA, Madden RJ, Strong FM, Woolley DW (1938). “The isolation and identification of the anti-black tongue factor” (PDF). J. Biol. Chem. 123 (1): 137–49. 
  94. Jump up ^ Axelrod AE, Madden RJ, Elvehjem CA (1939). “The effect of a nicotinic acid deficiency upon the coenzyme I content of animal tissues” (PDF). J. Biol. Chem. 131 (1): 85–93. 
  95. Jump up ^ Kornberg A (1948). “The participation of inorganic pyrophosphate in the reversible enzymatic synthesis of diphosphopyridine nucleotide” (PDF). J. Biol. Chem. 176 (3): 1475–76. PMID 18098602. 
  96. Jump up ^ Friedkin M, Lehninger AL (1 April 1949). “Esterification of inorganic phosphate coupled to electron transport between dihydrodiphosphopyridine nucleotide and oxygen”. J. Biol. Chem. 178 (2): 611–23. PMID 18116985. 
  97. Jump up ^ Preiss J, Handler P (1958). “Biosynthesis of diphosphopyridine nucleotide. I. Identification of intermediates”. J. Biol. Chem. 233 (2): 488–92. PMID 13563526. 
  98. Jump up ^ Preiss J, Handler P (1958). “Biosynthesis of diphosphopyridine nucleotide. II. Enzymatic aspects”. J. Biol. Chem. 233 (2): 493–500. PMID 13563527. 
  99. Jump up ^ Bieganowski, P; Brenner, C (2004). “Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans”. Cell 117 (4): 495–502. doi:10.1016/S0092-8674(04)00416-7. PMID 15137942. 
  100. Jump up ^ Chambon P, Weill JD, Mandel P (1963). “Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme”. Biochem. Biophys. Res. Commun. 11: 39–43. doi:10.1016/0006-291X(63)90024-X. PMID 14019961. 
  101. Jump up ^ Clapper DL, Walseth TF, Dargie PJ, Lee HC (15 July 1987). “Pyridine nucleotide metabolites stimulate calcium release from sea urchin egg microsomes desensitized to inositol trisphosphate”. J. Biol. Chem. 262 (20): 9561–8. PMID 3496336. 
  102. Jump up ^ Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000). “Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase”. Nature 403 (6771): 795–800. Bibcode:2000Natur.403..795I. doi:10.1038/35001622. PMID 10693811. 

 

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