HBD Activity Research Articles

HbA2 levels in normal adults are influenced by two distinct genetic mechanisms

Using a genome-wide association study, we found that common inter-individual differences in haemoglobin A(2) (HbA(2) , α(2) δ(2) ) levels are largely governed by genetic factors (42% of variability). The influence of age (1%) and sex (4%) was small. HbA(2) levels were influenced by two loci: the HBS1L-MYB locus on chromosome 6q, which has been shown to have pleiotropic effects on other haematological traits; and a second locus surrounding HBB, the gene encoding β-globin. Our results suggest that HbA(2) levels in adults are influenced by two different biological processes: one via kinetics of erythropoiesis, and the other, via competition between HBB and HBD activity.

Increased Alpha-Hydroxybutyrate Dehydrogenase in Serum from Children with Measles

For treatment and prognostic evaluation of patients with measles, it is important to determine the source of the increase in serum alpha-hydroxybutyrate dehydrogenase (HBD; EC 1.1.99.6). Here we measured HBD and L-lactate dehydrogenase (LD; 1.1.1.27) activities in the serum of 18 children with measles and in 18 age-matched control patients with bronchopneumonia. HBD and LD activities in the measles patients were significantly higher than those in control subjects (P less than 0.001). The HBD/LD ratio in the measles patients two to three days after the onset of rash was significantly lower than that in control subjects (P less than 0.001). The low HBD/LD ratio was similar to the ratio found in lymphocytes. The number of peripheral lymphocytes decreased markedly after the onset of rash. Our results suggest that increased serum HBD and LD activity is common in measles infection and that the increase originates from the destruction of infected lymphocytes rather than from myocardiac injury.

Activity of serum enzymes in puromycin aminonucleoside-induced nephrotic syndrome.

Total serum protein, serum albumin, total urine protein excretion, and the serum activity of several enzymes--aldolase (ALS), cholinesterase (CHS), leucine aminopeptidase (LAP), isocitrate dehydrogenase (ICD), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBD), creatine kinase (CK), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT)--were estimated in rats with nephrotic syndrome (NS) at 2, 4, 6, 8, 10, 12, 16, 20, and 30 days after a single injection of puromycin aminonucleoside (PAN). It was found that: (a) total serum protein and serum albumin diminished on day 4 and returned to control values on days 20 and 30, respectively; (b) total urine protein excretion rose on day 4, reached a peak value on day 8, and then fell substantially but still remained higher than control values on day 30; (c) ALS and CHS activities increased; (d) LAP, ICD, and AST activities showed a biphasic pattern, first increasing and then decreasing; (e) ALT, LDH, HBD, CK, and ALP activities decreased; and (f) GGT activity remained unchanged. The differences in the profiles of the enzyme activities suggest their independent regulation in experimental NS induced by PAN.

Improving effects obtained by the ovariectomy or treatment with tamoxifen of female diabetic rats over the function and enzyme activities of liver mitochondria.

In the present work we studied, in female chronic diabetic rats the effect of either the parenteral administration of tamoxifen (TAM) (500 micrograms.kg-1.day-1) for 15 days or the ovariectomy upon the respiration and oscillatory behaviour of intact mitochondria and the activities of 3-hydroxybutyrate dehydrogenase (HBD) and cytochrome c oxidase (Cox) of disrupted liver mitochondria. The treatment with TAM as well as the ovariectomy of diabetic animals significantly increased the respiratory control (RC) and the state 3 (S3) of respiration of intact liver mitochondria with the three substrates assayed (3-hydroxybutyrate, malate-glutamate and succinate). Both treatments also lowered significantly the damped factors of the oscillatory variation of liver intact mitochondria of diabetic rats. Moreover, the two above-mentioned treatments restored the activities of HBD and Cox of liver disrupted mitochondria to normal values. The effect of estrogens at level of its receptors in the modulation of liver mitochondrial function and liver HBD and Cox activities in chronic diabetes is discussed.

Total Lactate Dehydrogenase and Its Isozymes in Serum from Patients with Primary Carcinoma of the Ovary

Serum lactate dehydrogenase (LDH), its isozymes and alpha-hydroxybutyrate dehydrogenase (HBD) were examined in 57 patients with primary carcinoma of the ovary and compared to those in 220 patients with benign ovarian tumor. Serum LDH, LDH-4, LDH-5 and HBD in patients with ovarian carcinoma were significantly higher than those in patients with benign ovarian tumor. Except for the percent fraction of LDH-5, LDH activity, LDH-4 activity, percent fraction of LDH-4, LDH-5 activity and HBD activity in patients with ovarian carcinoma correlated significantly with stage of disease. The positive result of ovarian carcinoma was highest at LDH-4 activity (43.6%), followed by LDH activity (42.1%), HBD activity (34.6%), LDH-5 activity (32.7%), percent fractions of LDH-4 and LDH-5 (20.0%). On the other hand, the false-positive rate in patients with benign ovarian tumor was highest at LDH activity (12.7%), followed by HBD activity (10.0%), LDH-5 activity (8.6%), percent fraction of LDH-5 (8.2%), LDH-4 activity (6.8%) and percent fraction LDH-4 (3.6%). The detection rate for early ovarian carcinoma (stages I and II) was elevated from 4.5% by HBD activity alone to 50.0% by a combination assay of LDH, LDH-4, LDH-5 and HBD, while that for advanced ovarian carcinoma (stages III and IV) was elevated from 50.0% by HBD alone to 79.4% by the combination assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring by alpha-hydroxybutyrate dehydrogenase of human ovarian carcinoma grown in nude mice.

In order to establish that the tumor burden in nude mice bearing a xenografted human ovarian tumor can be assessed by measuring plasma levels of alpha-hydroxybutyrate dehydrogenase (HBD) (E.C. 1.1.1.30), the plasma HBD and the tumor volume were measured every week after inoculation of a human ovarian carcinoma cell line designated HR. About 3 weeks after tumor inoculation, all nude mice had a palpable tumor while elevated levels of HBD were observed in a half of the mice at that time. Thereafter the HBD levels rose with increasing tumor volume. There was a quantitative linear relationship between the tumor weight and HBD activity per mouse. When 40 micrograms of cisplatin (about 2 mg/kg) was administered i.p. every week for 5 weeks 2 weeks after inoculation, plasma levels of HBD were significantly decreased on day 27 compared to those in untreated nude mice. Decreases in the HBD levels during treatment with cisplatin occurred 7 days prior to changes in tumor volumes. Further, removal of local tumor mass resulted in a marked decrease in HBD levels on day 1 after surgery and the HBD levels in nude mice which had no recurrent tumor fell into the normal range 8 days after surgery.

Modified oscillation behavior and decreased d-3-hydroxybutyrate dehydrogenase activity in diabetic rat liver mitochondria

One month after induction of diabetes in adult white rats with streptozotocin or 4–10 months after its induction by pancreatectomy (in every case glycemia was over 3 g/liter), the following alterations were observed in liver mitochondria: (a) a decrease of amplitude and an increase of the damping factor of volume oscillations induced by potassium ions and valinomycin; (b) a 50% decrease of d-3-hydroxybutyrate dehydrogenase (HBD) activity in mitochondria disrupted by repeated freeze-thawing; (c) a similar decrease in the rate of d-3-hydroxybutyrate oxidation by intact mitochondria; (d) a significant increase of cytochrome oxidase activity and cytochrome aa 3 content. Measurement of succinate dehydrogenase and NADH dehydrogenase activity, the cytochrome b, c 1, and c content, and the P:O ratio for mitochondria oxidizing d-3-hydroxybutyrate did not reveal significant differences between control and diabetic rat mitochondria. In the streptozotocin-injected rats, the variation of HBD activity and the modification of the mitochondrial oscillation pattern were time-dependent phenomena, both effects reaching their maximal expression about 1 month after the onset of diabetes. The variation of HBD activity followed a biphasic course, since it rose to above the control level during the first 2 weeks of diabetes, then fell progressively to about half the control value after the third week. Treatment of diabetic rats with NPH insulin (5 IU twice daily, for 3 days, reinforced by the same dose 45 min before sacrifice) restored the mitochondrial oscillation pattern, HBD activity, and rate of d-3-hydroxybutyrate oxidation by intact mitochondria to their normal values.

Comparison of three serum α-hydroxybutyrate dehydrogenase procedures for lactate dehydrogenase isoenzyme discrimination

Three recently proposed methods for the assay of α-hydroxybutyrate (2-oxobutyrate) dehydrogenase (HBD) activity in serum were assessed to determine which one would give the most useful discrimination between the lactate dehydrogenase (LD) isoenzymes. The 2-oxobutyrate concentration and temperature for these procedures were 3.3 mmol/l at 30°C, 12 mmol/l at 30°C and 15 mmol/l at 37°C. LD isoenzyme activity values obtained by thin-layer agarose electrophoresis were compared with HBD activity results by linear regression analysis. The best, statistically significant, correlation of LD-1 with HBD activities was obtained with 3.3 mmol/l at 30°C (regression coefficient, 0.92; correlation coefficient, 0.98).

Interaction of rat liver 3- d-(—)-hydroxybutyrate apodehydrogenase with phospholipids

The interaction of phospholipids with pure, catalytically inactive rat liver 3- d-(—)-CoA hydroxybutyrate apodehydrogenase (apoHBD) was examined, (a) A relationship could be established between density of packing of phospholipid molecules at the interface and apoHBD activation, namely, the larger the area per polar head, the higher the lipid molar efficiency. In this context, codispersion of lecithins with phospholipids that were inactive or scarcely active per se, such as phosphatidylethanolamine and lysophosphatidylcholine (miristoyl; Iysod 14) increased the activating efficiency of lecithins, (b) ApoHBD formed tightly bound, catalytically active complexes with lecithin liposomes and micelles (diC 10 + lysoC 14; cetylphosphorylcholine), but a phospholipid-water interface was not essential for HBD activity since a molecular dispersion of diheptanoyl lecithin (diC 7) activated apoHBD to a limited extent. ApoHBD formed loosely bound, catalytically inactive complexes with multilayer vesicles, but HBD activity could be restored by sonication or by adding liposome to those complexes. Unlike liposomes and micelles, apoHBD interaction with multilayer vesicles did not involve a hydrophobic contribution, which was apparently necessary for apoHBD activation, (c) LysoC 14, did 10 + lysoC 14, and cetylphosphorylcholine micelles activated apoHBD but diC 7 micelles inhibited the HBD activity of the apoHBD-diC 7 (monomer) complex. The inhibition decreased when the medium ionic strength was increased. Liposomes and diCi 10 + lysoC 14 micelles activated and stabilized apoHBD much more efficiently than pure lysoC 14 or cetylphosphorylcholine micelles, (d) The mode of aggregation of the activating phospholipid strongly affected the kinetics of the HBD reaction. With liposomes the reaction showed an initial lag (or induction) period whose duration varied over a range of 3 to 15 min, depending on the activating phospholipid; with diC 7 monomers and micelles the kinetics was linear throughout, while with multilayer vesicles the lag was virtually infinite since HBD activity was insignificant, (e) Energies of activation for apoHBD-diC 14 complexes, either below or above the lecithin gel-to-liquid crystalline transition temperature were not significantly different, in accordance with apoHBD interaction with the proximal end of the hydrocarbon chains, that is, the less subject to phase transitions. With a diC 14-substituted mitochondrial preparation, however, no HBD activity was detected below 24 °C (near the gel-to-liquid crystalline transition temperature of diC 14), thus indicating that, in the inner membrane, apoHBD interacts with the whole length of the fatty acyl chain and, consequently, is sensitive to phase transition.

Determination of isoenzyme contents of lactic dehydrogenase activity and 2-hydroxybutyric dehydrogenase activity in lactic dehydrogenase preparations

In this inestigation, a determination of the isoenzyme contents of LDH and HBD activities in lactate dehydrogenase preparations and the differences in the interaction of these preparations with NAD analogues were examined. The results obtained were as follows. 1. 1. The activity ratio between oxidation and reduction in LDH reactions is shown to be similar in both H 4 and M 4 preparations, whereas for HBD activity, the ratio seems to be lower in the M 4 preparation than in H 4(H 4/M 4 = 1 2 ). 2. 2. NAD and its analogues (NXD, TNAD, and TNXD) are shown to be useful coenzymes for the LDH reaction, while 3-acetyl derivatives appear to be unsuitable for this purpose because of their lower activity. HBD activity with 3-acetyl NXD is shown to be higher than with TNAD or TNXD. Among these NAD analogues, 3-acetyl NXD gives the highest HBD activity, especially in the M 4 preparation. 3. 3. The LDH activity of H 4 relative to M 4 preparations has been shown to be maximal when 450 mM lactic acid with NAD or 15 mM lactic acid with TNXD are used. Under these conditions, the contents of LDH subunits can be estimated with considerable reliability. As to HBD activity, the content of LDH subunit having HBD activity has been estimated by determining the enzyme activity under conditions in which either 300 mM 2-hydroxybutyrate with 3-acetyl NXD or 15 mM 2-hydroxybutyrate with NAD are employed.

THE ENZYMOLOGICAL STUDY IN GASTRIC MUCOSA

LDH, HBD, LAP, γ-GTP, ALP and ACP activity levels and LDH isoenzymes in gastric mucosa were studied.The materials were obtained by endoscopic biopsy from the stomach. Thirteen patients who were determined endoscopically normal, 26 patients who had gastric ulcer and 29 patients who had cancer were investigated. The results were as follows : 1. In caner tissue, the activity levels of five enzymes except HBD were higher than those of normal gastric mucosa. Some differences in the activity levels of those enzymes were observed in histologically different types.2. LDH-M subunit values (%) were relatively higher in well differentiated cancer tissue than in poorly differetiated one.3. Statistical study revealed no difference between cancer lesions and the neighbouring mucosa about LDH isoenzyme.4. Only in the upper part of the greater curvature, LDH-M subunit values showed significantly higher in cancer bearing gastric mucosa than in normal gastric mucosa.5. The older the age of patients, the less the activity levels of LDH, HBD, LAP and γ-GTP were observed. As the age progressed, the ratio of LDH-M subunits was increased, especially in the upper part of the lesser curvature.

Optimal α-Oxobutyrate Concentration for Assay of α-Hydroxybutyrate Dehydrogenase Activity in Normal and Pathological Sera at 30 °C

Abstract Optimal concentration of substrate, α-oxobutyrate, for determination of α-hydroxybutyrate dehydrogenase (HBD) activity in normal and pathological sera at 30 °C (with a centrifugal analyzer) is 12 mmol/ liter. With this substrate concentration, HBD activity averaged 146% of that found with the suboptimal concentration, 3.3 mmol/liter, usually used. Furthermore, day-to-day precision was significantly better. HBD/LD ranges (LD, lactate dehydrogenase), determined for sera from patients with myocardial infarction and liver disease, did not overlap and were similar to those established by Elliot et al. [Clin. Sci. 23, 305 (1962)], who used a suboptimal α-oxobutyrate concentration of 3.3 mmol/liter at 25 °C. At 30 °C the mean HBD/LD ratios for sera from patients with myocardial infarction were most different from those for patients with liver disease when the optimal concentration of α-oxobutyrate was used.

Studies on the pre and post-operative management of nutrition from the digestive diseases especially on the changes of serum LDH and HBD activity, blood pyruvic acid level and serum free amino acid pattern

Studies on the pre and post-operative management of nutrition from the digestive diseases especially on the changes of serum LDH and HBD activity, blood pyruvic acid level and serum free amino acid pattern

Correlation of Serum and Urine Enzyme Activity in Patients with Acute Myocardial Infarction

Abstract A correlation was made between the urinary excretion of GOT, GPT, LDH, HBD, and acid and alkaline phosphatase and their serum activity in 18 suspected cases of myocardial infarction. The diagnoses were made by a cardiologist without knowledge of the enzyme assays. The study included 2 cases of nontransmural infarction; 5 cases that had not sustained an infarction served as controls. Elevations of serum GOT, LDH, and HBD were found in 10 of 11 cases of transmural infarction, GPT and acid phosphatase in 5, and alkaline phosphatase in 7. Elevations in serum acid phosphatase were also found in the control group, and perhaps were related to the anticoagulation therapy. Urinary GOT and GPT activity was variable. Urinary LDH and HBD were elevated in 6 of the transmural infarction cases, usually when serum LDH and HBD activity was decreasing. Urinary acid phosphatase activity was essentially normal; but urinary alkaline phosphatase increased in 10 of the transmural infarction cases, and the average value remained high for more than 5 weeks. The only index that was elevated in all cases of acute transmural infarction was L-phenylalanine inhibition of urinary alkaline phosphatase activity.

Serum alpha-hydroxybutyrate dehydrogenase activity in cancer of digestive organs

We previousely reported that, among those patients showing high serum lactate dehydrogenase (S-LDH) activity, those with myocardial infarction and progressive muscular dystrophy also high serum alphahydroxybutyrate dehydrogenase (S-HBD) activity and those with hepatobiliary diseases showed normal value. The present study deals with an investigation of S-HBD activity in 192 patients with malignant tumors of digestive and other organs. Increased S-HBD activity was shown by 6 among 70 cases of cancer of the stomach, 4 among 21 of cancer of the pancreas, 10 among 20 of primary cancer of the liver, 6 among 10 of metastatic cancer of the liver and none among 8 of cancer of the biliary tract . Some of the patients with cancer of the liver, especially pr imary cancer, showed remarkable increase in S-HBD activity. Thus we did not find S HBD activity to be so sensitive in cancer patients as S-LDH activity. S-HBD/S-LDH ratio was found to be high in myocardial infraction and progressive muscular dystrophy, and low in hepatobiliary diseases, and, 62% of cancer patients also showed low ratios. The result of our study of a small number of cases by cellulose acetate electrophoresis showed that the fast:moving S-LDH isozymes were relatively increased in patients with stomach and pancreas cancer in spite of their low S-HBD/S-LDH ratios.

SERUM ENZYME ACTIVITIES IN ENDOTOXIN SHOCK.

The glutamic oxalacetic transaminase (GOT), lactic dehydrogenase (LDH), α-hydroxybutyric dehydrogenase (HBD), and creatine phosphokinase (CPK) activities in the serum of 13 rabbits have been studied upon intravenous Escherichia coli endotoxin administration. The systolic blood pressure and the rectal temperature of the animals were recorded at each blood sampling. A prompt rise of the serum GOT, LDH, and HBD activities occurred, that of the serum GOT being the most marked. No increase of serum CPK activity during the shock was noted. The observed elevations subsided within 48 hr after endotoxin administration. The liver is suggested as the most likely point of enzyme release into the blood; the effect might be caused by tissue hypoxia coupled with catecholamine leakage.

SERUM ENZYME ACTIVITY IN LATE PREGNANCY, AT DELIVERY, AND DURING PUERPERIUM.

Serum creatine phosphokinase (CPK), a-hydroxybutyric dehydrogenase (HBD), glutamic oxalacetic transaminase (GOT) and lactic dehydrogenase (LDH) activities were measured in late pregnancy some days before and during delivery, and 5 days after delivery in a series of 30 mothers and their 15 newborn infants. Furthermore, daily determinations of these enzymes were made in 10 mothers up to the fourteenth postpartum day.Elevated CPK activity in the serum was observed in late pregnancy, particularly during and some days after delivery. LDH and HBD showed some elevation at delivery. GOT had no tendency 30 rise in these circumstances. In newborn infants the serum LDII and HBD activities were about twice as high as those seen in their mothers, but the serum GOT activity was not greater in the umbilical cord than in the maternal serum. It seems possible that the increase of CPK activity in the serum may partly be accounted for by release from the uterus musculature, which was found to have increased CPK activity in ...

Serum α-hydroxybutyric dehydrogenase (HBD) in myocardial infarction: Comparison with glutamic oxalacetic transaminase (GOT) and lactic dehydrogenase (LDH) ∗

In a comparative study, simultaneous determinations of the α-hydroxybutyric dehydrogenase (HBD), GOT and LDH enzyme activities were made from 369 serum samples in serial analyses in 60 clinically diagnosed cases of recent myocardial infarction. Elevation of serum HBD occurred more frequently than a concurrent rise in serum GOT or LDH. Enhanced serum HBD activity persisted for a longer time than the corresponding rise in serum GOT or LDH. It is suggested that the determination of HBD activity offers a promising aid in the detection of myocardial infarction, especially since the measurement of this enzyme is easy.