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T K Li

Publications and source records attributed to T K Li.

At least 289 records · Page 16Linked to original sources
PubMed1979

pH-independent inhibition of plasma angiotensin I degradation: implications for renin assay.

Valid enzymatic assay of plasma renin (EC 3.4.99.19) requires complete inhibition of enzymes that destroy angiotensin I. Historically, the degree of such inhibition has varied with assay pH and with the combination of protease inactivators employed. To circumvent this problem, we studied the effects of several protease inactivators on both the formation and degradation of angiotensin I by human plasma at pH 5.5 and at pH 7.4. While several reagent combinations effectively suppressed the rate of angiotensin I disappearance at one of the two pH values, three combinations of phenylmethylsulfonyl fluoride with chelating agents accomplished this at both pH values. Of these, however, only the combination of 5 mmol/l ethylenediamine tetraacetate, 1.5 mmol/l 8-hydroxyquinoline, and 7.5 mmol/l phenylmethylsulfonyl fluoride also maximized the rate of angiotensin I formation at both pH 5.5 and 7.4. Thus, the use of the latter reagent combination would facilitate comparison of renin assays performed at different pH values and would permit standardization of the protease inactivators employed in such assays.

Angiotensin I↗
PubMed1979

Transport and metabolism of thiamin in isolated rat hepatocytes.

This study examines thiamin transport in isolated rat hepatocytes and its relationship to thiamin phosphorylation. In an Na+ medium, [35S]thiamin, 3 microM, was accumulated rapidly by the cells, and a near study state intra-/extracellular distribution ratio of 3 was attained in 1 min. However, the uptake of radioactivity continued to increase with time owing principally to the accumulation of [35S]thiamin pyrophosphate (TPP). In a choline, Li+ or K+ medium, the steady state intra-/extracellular distribution ratio of [35S]thiamin was decreased to less than or equal to 1.1. Accordingly, the rate of formation of [35S]TPP also decreased. Ouabain and uncouplers of oxidative phosphorylation significantly lowered the distribution ratio of intra-/extracellular [35S]thiamin. These data indicate that thiamin transport in liver is concentrative, Na+-dependent, and dependent on biological energy. Additionally, they suggest that thiamin transport plays a significant role in governing the rate of synthesis of TPP. Neither pyrithiamin, an inhibitor of thiamin pyrophosphokinase nor o-benzoylthiamin disulfide, a permeable thiamin analog, affected the distribution ratio of intra-/extracellular [35S]thiamin, but preferentially inhibited the phosphorylation of [35S]thiamin. By contrast, amprolium primarily inhibited uptake. These data suggest that thiamin transport and phosphorylation can be differentiated by the action of appropriate inhibitors.

Animals↗
PubMed1978

Neurochemical and operant behavioral studies of a strain of alcohol-preferring rats.

The levels of serotonin (5-HT), 5-hydroxyindoleacetic acid, tyrosine (TYR), norepinephrine (NE), acetylcholine, GABA, glutamate (GLU), aspartate (ASP), alanine, glycine (GLY) and taurine were measured in the CNS of adult male rats selectively inbred to the F8 generation for alcohol preference (P) and non-preference (NP). With respect to the values found in the NP group, higher levels of 5-HT, GABA, GLU and GLY and lower levels of ASP were found in the diencephalon-mesencephalon (D-M) and higher levels of NE were found in the telencephalon (TEL) of the P group. The animals in the P and NP strains were further subdivided into two additional groups, one given only H2O (W) and the second given 10% ethanol (A) during a one week period, thereby producing four groups (NP-W, NP-A, P-W and P-A). With these conditions, the level of (a) TYR in the D-M was higher in the P-A and NP-A animals than in the P-W and NP-W groups respectively; (b) 5-HT in the TEL was higher in the NP-A group than NP-W group; and (c) GABA in the TEL was higher in the P-A than P-W animals. No differences were observed in the cerebellum between the two strains or between the subgroups within each strain. The present study also demonstrated that the P animals will work in an operant situation to obtain 10% ethanol, even when H2O is freely available, and will voluntarily bar-press up to 6-7 times for each ethanol reinforcement.

Alcohol Drinking↗
PubMed1978

Validation of the diagnostic value of plasma pyridoxal 5'-phosphate measurements in vitamin B6 nutrition of the rat.

The relationship of plasma pyridoxal 5'-phosphate (PLP) to PLP content of tissues and activities of PLP-dependent enzymes was examined to establish its value in assessing vitamin B6 nutrition. Weanling rats were fed ad libitum for 9 weeks purified diets which supplied 0, 4, 12, 24, and 100 micrograms of pyridoxine daily. Growth increased with increasing pyridoxine intake, reaching a maximum at 24 micrograms/day. Liver and brain PLP also increased, attaining maximal values at 12 micrograms. By contrast, muscle and plasma PLP did not saturate when vitamin B6 intake was increased to 100 micrograms. Erythrocytic holoenzyme activity of aspartate (Asp) aminotransferase became maximal with 24 micrograms but that of alanine (Ala) aminotransferase did not. Hepatic holoenzyme activities of Ala, Asp and tyrosine aminotransferases reached maximal values with only 4 micrograms vitamin B6 but that of serine dehydratase became maximal with 12 micrograms. Measurement of coenzyme saturability suggested that apoenzyme degradation, coenzyme affinity and PLP transfer determine the activities of these enzymes. It is concluded that plasma and muscle PLP behave as mobilizable storage pools and that plasma PLP is a sensitive and reliable indicator of vitamin B6 nutrition.

Animals↗
PubMed1977

Isolation of pi-alcohol dehydrogenase of human liver: is it a determinant of alcoholism?

HUMAN LIVER ALCOHOL DEHYDROGENASE (ALCOHOL: NAD(+) oxidoreductase, EC 1.1.1.1), homogeneous by physicochemical criteria, has been available in quantity only recently [Lange, L. G. & Vallee, B. L. (1976) Biochemistry 15, 4681-4686]. Until now, the biochemical basis of human alcohol metabolism had to be extrapolated from the properties and behavior of enzymes from other species, primarily horses and yeast. The biological determinants of human alcoholism have remained obscure, although recent evidence indicates a genetic predisposition, requiring delineation. A functionally distinct form of human liver alcohol dehydrogenase (ADH), which we have designated II-ADH, is provocative since, thus far, it seems to be unique to human beings. It has a high K(m) for ethanol and is remarkably insensitive (apparent K(I), 500 muM) to pyrazole and its derivatives, which are usually potent ADH inhibitors (K(I), 1 muM), a property that is the basis for the isolation of II-ADH. The affinity resin 4-[3-(N-6-aminocaproyl)aminopropyl]pyrazole-Sepharose binds all other known forms of ADH but not II-ADH, thereby separating it selectively by affinity chromatography. In turn, this has led to the establishment of its identity with that enzyme form which was previously known as the anodic band and characterized by a high K(m) for ethanol (20 mM at pH 7.5). The remarkable insensitivity of II-ADH to pyrazole inhibition has also permitted quantitation of its role in hepatic ethanol oxidation. At 5 mM ethanol, a saturating concentration for virtually all other forms of ADH, II-ADH contributes less than 15% to total ethanol oxidation. However, at intoxicating concentrations, e.g., 60 mM, it can account for as much as 40% of the total ethanol oxidation rate of liver, indicating a seemingly unique role for this enzyme form in ethanol elimination. Thus far, we have found the amount of II-ADH varies from liver to liver of individuals and is considerably more labile than the other molecular forms, phenomena whose inter- or independence requires further study. The isolation of human II-ADH advances efforts to recognize and understand biochemical mechanisms that may be biological determinants of alcoholism and alcohol-related disease states, now generally approached and managed largely as psychosocial disorders.

Alcohol Oxidoreductases↗
PubMed1976

The effects of ionophore A23187 on erythrocytes. Relationship of atp and 2,3-diphosphoglycerate to calcium-binding capacity.

The divalent cation ionophore, A23187, was employed as a means to load fresh human erythrocytes with calcium, and the capacity for accumulation was characterized. Erythrocytes exposed to A23187 in calcium-containing media rapidly accumulated calcium in millimolar quantities. The final cellular concentration was dependent upon medium calcium concentration and the size of the cellular organophosphate pool. When ATP and 2,3-diphosphoglycerate contents were depleted or repleted, the cellular calcium content changed proportionally. Calcium loading of fresh erythrocytes produced no discernible change in the cellular concentrations of ATP or 2,3-diphosphoglycerate. Calcium accumulation was also accompanied by loss of cellular potassium and H2O, deterioration of cell filterability, and spheroechinocytic transformation.

Adenosine Triphosphate↗
PubMed1976

Alcohol metabolism in American Indians and whites. Lack of racial differences in metabolic rate and liver alcohol dehydrogenase.

To investigate alleged racial differences in alcohol tolerance, we measured the rate of ethanol metabolism in 30 American Indians and 30 whites. The mean rates of alcohol metabolism were virtually identical in the two groups: 92 +/- 3 mg of ethanol metabolized per kilogram of body weight per hour for the Indians versus 93 +/- 3 for the whites (mean +/- S.E.M.). Similarly, a comparison of liver alcohol dehydrogenase specific activity and isoenzyme pattern in biopsy specimens from seven American Indians and six whites revealed no racial differences. Biopsy specimens from the Indians demonstrated a mean specific enzymatic activity of 0.073 +/- 0.004 mumoles of ethanol oxidized per minute per milligram of soluble protein and from the whites, 0.082 +/- 0.009. These findings make it unlikely that alleged racial differences in response to alcohol can be explained on the basis of racial differences in the rate of alcohol metabolism.

Adolescent↗
PubMed1976

The relationship of serum ionized and total calcium in primary hyperparathyroidism.

Ionized and total calcium concentrations were measured in the same serum samples of 48 patients with primary hyperparathyroidism in order to compare diagnostic accuracy and sensitivity and to determine the intra-individual variation of these parameters in this disorder. In 149 samples, 0.7 per cent of serum ionized calcium and 7.4 per cent of total calcium determinations were within the normal range (mean +/- 2 S.D.). However, all patients exhibited abnormally elevated values upon repeated testing. Ionized and total calciums were significantly correlated both preoperatively (r=0.85 and p less than 0.001) and postoperatively (r greater than 0.9). Heterogeneous and abnormally large variations of both measurements were noted in these patients. It is concluded that the superior precision of the method for ionized calcium determination renders it more accurate than total calcium for the diagnosis of primary hyperparathyroidism. The disturbance of calcium homeostasis is reflected in both calcium and its ionic fraction in serum.

Calcium↗