Acetoacetyl-CoA reductase activity of lactating bovine mammary fatty acid synthase.

Dodds, Peter F.; Guzman, Monica; Chalberg, S C; Anderson, Gregory J.; Kumar, Soma

doi:10.1016/s0021-9258(19)69160-x

Cited by 41 publications

(14 citation statements)

References 27 publications

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“…As expected, fat percentage and FPR significantly increased with increasing ketone body concentrations in milk. The fat percentage and FPR increase is due to the strong body fat mobilization in the period of a negative energy balance, and the utilization of BHB for fatty acid synthesis in the mammary gland (Dodds et al, 1981). SCS increased with increasing BHB and acetone concentration.…”

Section: Statistical Associations Between Acetone and Bhb With Test-day Production Traitsmentioning

confidence: 99%

Genetic and nongenetic profiling of milk β-hydroxybutyrate and acetone and their associations with ketosis in Holstein cows

Klein

Scheper

May

et al. 2020

Journal of Dairy Science

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Ketosis is a metabolic disorder of increasing importance in high-yielding dairy cows, but accurate population-wide binary health trait recording is difficult to implement. Against this background, proper Gaussian indicator traits, which can be routinely measured in milk, are needed. Consequently, we focused on the ketone bodies acetone and β-hydroxybutyrate (BHB), measured via Fourier-transform infrared spectroscopy (FTIR) in milk. In the present study, 62,568 Holstein cows from large-scale German co-operator herds were phenotyped for clinical ketosis (KET) according to a veterinarian diagnosis key. A sub-sample of 16,861 cows additionally had first test-day observations for FTIR acetone and BHB. Associations between FTIR acetone and BHB with KET and with test-day traits were studied phenotypically and quantitative genetically. Furthermore, we estimated SNP marker effects for acetone and BHB (application of genome-wide association studies) based on 40,828 SNP markers from 4,384 genotyped cows, and studied potential candidate genes influencing body fat mobilization. Generalized linear mixed models were applied to infer the influence of binary KET on Gaussian-distributed acetone and BHB (definition of an identity link function), and vice versa, such as the influence of acetone and BHB on KET (definition of a logit link function). Additionally, linear models were applied to study associations between BHB, acetone and test-day traits (milk yield, fat percentage, protein percentage, fat-to-protein ratio and somatic cell score) from the first test-day after calving. An increasing KET incidence was statistically significant associated with increasing FTIR acetone and BHB milk concentrations. Acetone and BHB concentrations were positively associated with fat percentage, fat-toprotein ratio and somatic cell score. Bivariate linear animal models were applied to estimate genetic (co) variance components for KET, acetone, BHB and testday traits within parities 1 to 3, and considering all parities simultaneously in repeatability models. Pedigree-based heritabilities were quite small (i.e., in the range from 0.01 in parity 3 to 0.07 in parity 1 for acetone, and from 0.03-0.04 for BHB). Heritabilites from repeatability models were 0.05 for acetone, and 0.03 for BHB. Genetic correlations between acetone and BHB were moderate to large within parities and considering all parities simultaneously (0.69-0.98). Genetic correlations between acetone and BHB with KET from different parities ranged from 0.71 to 0.99. Genetic correlations between acetone across parities, and between BHB across parities, ranged from 0.55 to 0.66. Genetic correlations between KET, acetone, and BHB with fatto-protein ratio and with fat percentage were large and positive, but negative with milk yield. In genome-wide association studies, we identified SNP on BTA 4, 10, 11, and 29 significantly influencing acetone, and on BTA 1 and 16 significantly influencing BHB. The identified potential candidate genes NRXN3, ACOXL, BCL2L11, HIBADH, KCNJ1, and PRG4 are involv...

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Section: Statistical Associations Between Acetone and Bhb With Test-day Production Traitsmentioning

confidence: 99%

Genetic and nongenetic profiling of milk β-hydroxybutyrate and acetone and their associations with ketosis in Holstein cows

Klein

Scheper

May

et al. 2020

Journal of Dairy Science

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“…Geishauser et al (1988) reported that the correlation coe cient between BBAC and MBAC were from 0.00 to 0.87. BHBA can be utilised by the mammary gland for fatty acids synthesis and converted to butyrate (Dodds et al 1981;Du eld 2000) that is why MBAC is only 10-15% of BBAC, possibly because of the ketone body's role in fat metabolism in the udder (Andersson 1984). These uctuations in MBAC in contrast to BBAC may be a reason for the difference of BSCK from MSCK1 and MSCK2 in the present study.…”

Section: )mentioning

confidence: 56%

Blood and Milk Beta-Hydroxybutyric Acid Concentrations and Association of Subclinical Ketosis With Postpartum Health Disorders, Culling Rate, Body Condition Score, Parity and Milk Production in Holstein, Simmental, Montbeliard and Holstein-Crossbreed

Aksoy

Denız²,

Demir

et al. 2021

Preprint

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A total of 300 dairy cows were randomly enrolled from 11 dairy farms in Turkey. The beta-hydroxybutyric acid concentration (BAC) was tested in the blood (BBAC) and individual milk (MBAC) samples at postpartum week 2 (PPW2) and week 4 (PPW4) for the detection of subclinical ketosis (SCK) in Holstein, Montbeliard, Simmental and Holstein-Crossbred (HC; only BBAC). The prevalence of BSCK (BBAC ≥ 1.2 mmol/L), MSCK1 (MBAC = 100 µmol/L), MSCK2 (MBAC ≥ 200 µmol/L) and MSCK1/2 (≥ 100 µmol/L) was 8.3, 11.8, 5.8 and 17.3% at PPW2 and 4.7, 4.9, 6.9 and 11.9% at PPW4 in Holstein respectively. SCK was not observed in Simmental and HC. The prevalence of BSCK and MSCK1 at PPW2 were 4.3 and 43.5% in Montbeliard respectively. Primiparous Montbeliard and Holstein had significantly higher MBAC at PPW2 than PPW4. Overall, HC and Montbeliard had significantly lower BBAC. Cows having body condition scores 2 and 4 at calving had higher MBAC at PPW2 and 4 that was associated significantly with metritis and multiple diseases. Holstein with BCS4 at calving had higher BBAC at PPW2 and 4. Holstein with SCK was more likely to develop postpartum metabolic health disorders (PPHD) in 90 days in milk (90DIM). MSCK1 did not associate milk production loss in Montbeliard and Holstein. Holstein with both BSCK and MSCK2 at PPW2 had a 6.7 kg average daily milk yield loss in 90DIM. Conclusively, SCK was not observed in Simmental and HC, and MSCK1 didn’t cause PPHD and milk yield loss in Montbeliard. BSCK and MSCK2 created a significant risk for PPHD and milk production loss in Holstein.

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“…We decided to investigate the possibility of using suitable substrates for some of the individual reactions and monitoring them spectrophotometrically through the consumption of NADPH as described in Dodds et al. [26] for the bovine enzyme. Therefore, acetoacetyl‐CoA was used to monitor KR, β‐hydroxybutyryl‐CoA was used to monitor the activity of DH, and crotonoyl‐CoA was used to monitor the activity of ER.…”

Section: Resultsmentioning

confidence: 99%

Discovery of GSK837149A, an inhibitor of human fatty acid synthase targeting the β‐ketoacyl reductase reaction

et al. 2008

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GSK837149A has been identified as a selective inhibitor of human fatty acid synthase (FAS). The compound was first isolated as a minor impurity in a sample found to be active against the enzyme in a high‐throughput screening campaign. The structure of this compound was confirmed by NMR and MS studies, and evaluation of the newly synthesized molecule confirmed its activity against FAS. The compound and other analogs synthesized, all being symmetrical structures containing a bisulfonamide urea, act by inhibiting the β‐ketoacyl reductase activity of the enzyme. GSK837149A inhibits FAS in a reversible mode, with a Ki value of ∼ 30 nm, and it possibly binds to the enzyme–ketoacyl‐ACP complex. Although initial results suggest that cell penetration for these compounds is impaired, they still can be regarded as useful tools with which to probe and explore the β‐ketoacyl reductase active site in FAS, helping in the design of new inhibitors.

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Acetoacetyl-CoA reductase activity of lactating bovine mammary fatty acid synthase.

Cited by 41 publications

References 27 publications

Genetic and nongenetic profiling of milk β-hydroxybutyrate and acetone and their associations with ketosis in Holstein cows

Genetic and nongenetic profiling of milk β-hydroxybutyrate and acetone and their associations with ketosis in Holstein cows

Blood and Milk Beta-Hydroxybutyric Acid Concentrations and Association of Subclinical Ketosis With Postpartum Health Disorders, Culling Rate, Body Condition Score, Parity and Milk Production in Holstein, Simmental, Montbeliard and Holstein-Crossbreed

Discovery of GSK837149A, an inhibitor of human fatty acid synthase targeting the β‐ketoacyl reductase reaction

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