Adenosine triphosphate (ATP) regeneration systems are essential for efficient biocatalytic phosphoryl transfer reactions. Polyphosphate kinase (PPK) is a versatile enzyme that can transfer phosphate groups among adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, and polyphosphate (Poly P). Utilization of PPK is an attractive solution to address the problem of ATP regeneration due to its ability to use a variety of inexpensive and stable Poly P salts as phosphate group donors. This review comprehensively summarizes the structural characteristics and catalytic mechanisms of different types of PPKs, as well as the variations in enzyme activity, catalytic efficiency, stability, and coenzyme preference observed in PPKs from different sources. Moreover, recent advances in PPK-mediated ATP regeneration systems and protein engineering of wild-type PPK are summarized.
Adenosine Triphosphate/metabolism* ; Adenosine Monophosphate ; Polyphosphates/metabolism* ; Catalysis ; Regeneration

Cyclic adenosine monophosphate (cAMP) is one of the significant and conserved second messengers in mammals, and it participates in regulating the developmental and physiological functions of various organs and tissues through transducting extracellular signals. Studies have shown that the process of meiosis in female mammalian oocytes is closely related to the level of cAMP and strictly regulated. In oocytes, cAMP is mainly synthesized by adenylate cyclase 3 (AC3) and degraded by phosphodiesterase 3A (PDE3A), both of which jointly regulate the level of cAMP in oocytes and play important roles in the follicular development and oogenesis of female ovaries. It has been well illuminated that high level of cAMP in the cytoplasm of oocytes in growing follicles could maintain the arrest of the first meiotic of oocytes for a long time. The oocytes will resume meiosis and mature either when the synthesis of cAMP is down-regulated, or when cAMP is degraded by PDE3A. In recent years, the novo physiological functions of cAMP in oogenesis have been reported. To better understand the regulatory role and mechanism of cAMP in mammalian gametogenesis, this paper reviews the relevant research regarding the relationship between cAMP and germ cell development.
Adenosine Monophosphate ; Animals ; Cyclic AMP ; Female ; Mammals ; Meiosis ; Oocytes ; Oogenesis

Adenosine 5'-monophosphate-activated protein activated protein kinase (AMPK), a heterotrimeric complex, is an important kinase to regulate glycolipid metabolism and energy balance involved in a variety physiological processes in human body. Many research indicated that the function and activity of AMPK were closely related to inflammation, diabetes and cancers. Recent reports show that inhibition of metformin (a first-line drug) on hepatic glucose in patients with hyperglycemia is associated with AMPK pathway, suggesting that targeting AMPK may be one of the effective strategies for the prevention and treatment of a variety of chronic diseases. Here, we review research progress on the structure, activation and regulation of AMPK in glycolipid metabolism to provide an insight into the basic and clinical research of diabetes therapy.
AMP-Activated Protein Kinases ; Adenosine ; Adenosine Monophosphate ; Energy Metabolism ; Enzyme Activation ; Glycolipids ; Humans

PURPOSE: Tribulus terrestris has been used as an aphrodisiac. However, little is known about the effects and mechanism of action of T. terrestris on penile erection. Therefore, the effect of a T. terrestris extract and the mechanism of action of the extract on relaxation of the corpus cavernosum (CC) were investigated. The erectogenic effects of an oral preparation of the extract were also assessed. MATERIALS AND METHODS: The relaxation effects and mechanism of action of the T. terrestris extract on rabbit CC were investigated in an organ bath. The intracavernous pressure (ICP) was calculated after oral administration of the extract for 1 month to evaluate whether the relaxation response of the CC shown in the organ bath occurred in vivo. Additionally, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in the CC by immunoassay. Smooth muscle relaxation was expressed as the percentage decrease in precontraction induced by phenylephrine. The ICP was also assessed in rats after oral administration of the extract for 1 month, and changes in concentrations of cGMP and cAMP were monitored. RESULTS: Concentration-dependent relaxation effects of the extract on the CC were detected in the organ bath study. Relaxation of the CC by the T. terrestris extract was inhibited in both an endothelium-removed group and an L-arginen methyl ester pretreatment group. The ICP measured after oral administration of the T. terrestris extract for 1 month was higher than that measured in the control group, and a significant increase in cAMP was observed in the T. terrestris extract group. CONCLUSIONS: The T. terrestris extract induced concentration-dependent relaxation of the CC in an organ bath. The mechanism included a reaction involving the nitric oxide/nitric oxide synthase pathway and endothelium of the CC. Moreover, in an in vivo study, the T. terrestris extract showed a significant concentration-dependent increase in ICP. Accordingly, the T. terrestris extract may improve erectile function.
Adenosine Monophosphate ; Administration, Oral ; Animals ; Baths ; Endothelium ; Guanosine Monophosphate ; Immunoassay ; Male ; Muscle, Smooth ; Penile Erection ; Phenylephrine ; Rats ; Relaxation ; Tribulus

The incubation of adenosine 5-monophosphate(AMP) with the homogenates of the epidermis and dermis, which were obtained from the axilIary skin of osmidrosis (bromidrosis) patients, resulted in the formation of adenosine and inorganic phosphate (Pi) without further degradation, as demonstrated by paper chromatography. The conversion of AMP to adenosine in the skin was catalyzed by 5-nucleotidase and alkaline phosphatase. It was found that 5-nucleotidase was present both in the epidermis and dermis, being more active in the latter, and that the enzyme was responsible for more than 80% of the total AMP-hydrolyzing activity present in the skin homogenates. Alkaline phosphatase was shown to be present mainIy in the dermis. And its contribution to AMP hydrolysis was insignificant at pH 7.4. From these results, it is evident that AMP is converted to adenosine chiefly by 5-nucleotidase, which is present in the epidermis and dermis.
5'-Nucleotidase* ; Adenosine ; Adenosine Monophosphate* ; Alkaline Phosphatase ; Chromatography, Paper ; Dermis* ; Epidermis* ; Humans* ; Hydrogen-Ion Concentration ; Hydrolysis* ; Skin*

The aim of the present work is to investigate the existence of epistatic interactions possibly influencing psychotropic agents' response between rs6740584 within Cyclic adenosine monophosphate Response Element Binding (CREB) and rs12775799 within cAMP response element-modulator (CREM) variants in bipolar disorder (BD) and major depressive disorder (MDD). All BD and MDD patients were administered with the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAMD) at baseline and at endpoint, respectively. A multiple regression model was employed to investigate the existence of possible epistatic interactions between the two variants and diverse clinical factors including drug response in affective disorders. No significant epistatic interaction was observed between rs6740584 within CREB and rs12775799 within CREM on both symptom improvement and other clinical factors in affective disorders. Our preliminary results suggest that no epistatic interaction between rs6740584 within CREB and rs12775799 within CREM should exist on clinical improvement and clinical factors in affective disorders.
Adenosine Monophosphate ; Bipolar Disorder ; Depression ; Depressive Disorder, Major ; Humans ; Mood Disorders* ; Response Elements

Stress fractures typically result from repeated abnormal mechanical loading to the bones. In particular, multiple stress fractures may occur in patients with systemic disease, such as rheumatoid arthritis, osteoporosis, or osteoarthritis. Adefovir dipivoxil (ADV), a nucleotide analogue of adenosine monophosphate, very rarely causes severe hypophosphatemia when using a low dosage of 10 mg daily for treatment of chronic hepatitis B. To the best of our knowledge, in English literature, this is the first report of multiple stress fractures in a chronic hepatitis B patient who has been treated with a low dosage of ADV. We think it is important to consider that use of ADV in a patient with chronic hepatitis B could be a risk factor for stress fractures.
Adenosine Monophosphate ; Arthritis, Rheumatoid ; Fractures, Stress* ; Hepatitis B, Chronic* ; Humans ; Hypophosphatemia ; Osteoarthritis ; Osteoporosis ; Risk Factors

BACKGROUND AND OBJECTIVES: Phasic coronary flow velocity patterns and microvascular integrities are known to be prognostic factors in acute myocardial infarction (AMI). The use of a distal protection device during primary percutaneous coronary intervention (PCI) may preserve the microvascular integrity of the myocardium by preventing distal embolization of thrombotic materials. This study assessed the effects of such a device on microvascular integrity preservation through Doppler studies of the coronary flow velocities in AMI patients treated with primary PCI. SUBJECTS AND METHODS: A total of fifty-eight consecutive patients (mean age 54+/-15, 46 males) with ST segment-elevated AMI, who had undergone primary PCI within 24 hours after onset, were enrolled in the study. The subjects were divided into two groups: 30 patients with the PurcuSurge GuardWire Temporary Occlusion and Aspiration System and 28 without. The TIMI flows and TMP grades (TIMI myocardial perfusion grade) were evaluated. The coronary flow velocities were measured after PCI with a Doppler wire at the baseline, and also after intracoronary adenosine (24-48 microgram) induced hyperemia. The coronary flow velocity reserve (CFR), diastolic deceleration time (DDT) and microvascular resistance index (MVRI) were calculated. RESULTS: Between the two groups, no significant differences were found in the angiographic characteristics and CFR. In patients with a distal protection device, however, the post-PCI TMP grades were more favorable (TMP 0/1: 13.3%, TMP 2: 23.3%, TMP 3: 63.4% vs. TMP 0/1: 35.7%, TMP 2: 35.7%, TMP 3: 28.6%, p=0.023), with TMP grade 3 being most common (63.4% vs. 28.6%, p=0.010). These patients also exhibited lower bMVRI and hMVRI levels (4.33+/-2.22 vs. 5.55+/-2.36 mmHg.m-1.sec (p=0.047) and 2.39+/-1.40 vs. 3.14+/-1.36 mmHg.cm-1. sec (p=0.045), respectively), and longer bDDT and hDDT (679+/-273 vs. 519+/-289 msec (p=0.035) and 761+/-256 vs. 618+/-272 msec (p=0.044), respectively). CONCLUSIONS: Distal protection with the PurcuSurge GuardWire system may effectively preserve the microvascular integrity of the myocardium during primary PCI in AMI patients.
Adenosine ; Deceleration ; Humans ; Hyperemia ; Myocardial Infarction* ; Myocardium ; Percutaneous Coronary Intervention ; Perfusion ; Stents* ; Thymidine Monophosphate

OBJECTIVETo investigate the role of cyclic adenosine monophosphate(cAMP) in the regulation of intestinal epithelial barrier function under hypoxia.

METHODSIntestinal epithelial barrier was established by Caco-2 monolayers. Cells were divided into four groups: normoxia (Nx), normoxia plus Forskolin(Nx+FSK), hypoxia(Hx), hypoxia plus SQ22536(Hx+SQ22536). cAMP concentrations of different groups were assessed by cAMP enzyme immunoassay kit. RT-PCR and Western blotting were used to detect the mRNA and protein expressions of claudin-1 and occludin under normoxic and hypoxic condition. Caco-2 monolayers were grown on Millicell filters, and transepithelial electrical resistance(TER) was measured using a Millipore electric resistance system.

RESULTSThe concentration of cAMP under hypoxic conditions(Hx group) was higher compared with Nx group [(6.30±0.50) pmol/L vs. (2.38±0.18) pmol/L, P<0.01]. At the same time, both mRNA and protein expressions of claudin-1 and occluding were lower in Hx group than those in Nx group(all P<0.05). TER decreased by 76.30±0.64(P<0.01). When the monolayers were exposed to hypoxia plus SQ22536 (Hx+SQ22536 group), the concentration of cAMP was(2.12±0.23) pmol/L, which was lower than that under hypoxic conditions(Hx group, P<0.01). Both mRNA and protein expressions of claudin-1 and occludin were higher compared to Hx group (all P<0.01). TER increased by 32.96±2.16 (P<0.05).

CONCLUSIONWhen Caco-2 cells are exposed to hypoxia, barrier function, claudin-1 and occludin expression are diminished in parallel with a high level of intracellular cAMP compared with the normoxic condition. Inhibition of the intracellular cAMP level under hypoxia can maintain the intestinal epithelial function through regulating the claudin-1 and occludin expression and attenuate the permeability of intestinal mucosa.

Adenosine Monophosphate ; Caco-2 Cells ; Claudin-1 ; metabolism ; Humans ; Intestinal Mucosa ; metabolism ; Intestines ; Occludin ; metabolism

OBJECTIVEThis study aims to determine the influence of unilateral chewing on metabolic characteristics of masseter muscle fibers in rats and the regulatory effect of an adenosine monophosphate activated protein kinase (AMPK) signal pathway on metabolism.

METHODSRats were submitted to exodontia of all the right maxillary molars and divided into 2, 4, 6, and 8 weeks groups, and corresponding control groups were set as well. Sections were stained by nicotine adenine dinucleotide tetrazolim reductase(NADH-TRase) to demonstrate the types, proportion, and density of masseter muscle fibers. AMPKα1 and p-AMPK(Thr172) levels in bilateral masseter muscles were detected by Western blot.

RESULTSIn the 2-week group, the percentage of dark fibers augmented in the ipsilateral side, whereas the percentage of intermediary fibers in the contralateral side was increased accompanied by a decrease of light fibers, compared with the control group (P<0.05). The percentage of dark fibers was increased in the bilateral sides, whereas the percentage of dark fiber in the ipsilateral sides surpassed that of the contralateral sides in the 4, 6, and 8-week groups. The percentage of intermediary fibers was decreased in the bilateral sides in the 6 and 8-week groups (P<0.05). The percentage of light fibers was reduced in the ipsilateral sides in the 8-week group, whereas no alteration was observed in contralateral sides (P>0.05). In the ipsilateral sides, p-AMPK (Thr172)/AMPKα1 levels were increased in the 2 and 4-week groups (P<0.05), whereas no change was observed in the contralateral sides in either group (P>0.05).

CONCLUSIONSUnilateral chewing increases the oxidative metabolic ability in bilateral masseter muscle fibers especially in the non-working side accompanied with change of muscle fiber types. The improvement of aerobic metabolism ability is related to the AMPK signal pathway.
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AMP-Activated Protein Kinases ; Adenosine Monophosphate ; Animals ; Masseter Muscle ; Mastication ; Molar ; Protein Kinases ; Rats ; Tooth Extraction