PANTHENYL TRIACETATE TRANSFORMATION 7 six hours after application, the activities of ATP citrate lyase (-56%), dihydrolipoamide S-acetyltransferase (-52%), and the ATP-binding cassette, sub-family A (ABC1), member 12 (-62%), while after 24 hours there is a decrease in the activity of epidermal fatty acid- binding protein 5 (-65%). PTA stimulates, six hours after application, the activities of aconitase 2 mitochondrial, aconitate hydratase (+72%) and 3-hydroxy-3-methylglutaryl co- enzyme A synthase 2 (mitochondrial) (+218%), while after 24 hours there is an increase in malate dehydrogenase 2, NAD (mitochondrial) (+62%), 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (mitochondrial) (+201%), glucose phosphate isomerase (+55%), glucose-6-phosphate dehydrogenase (+68%), and cholesterol sulfotransferase (+60%). Globally it appears that PTA is pushing the citric acid cycle, glycolysis, and the mevalon- ate pathway, but also regulating the metabolism of lipids, interestingly pushing the syn- thesis of cholesterol sulfate with its implications on keratinocyte differentiation, while inhibiting lipid transport. When PAN was examined as depicted in Figure 7, seven main activities were detected (indicated by arrows). PAN decreases, six hours after application, the activities of 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (soluble) (-61%). PAN stimulates, six hours after application, aconitase 2 mitochondrial, aconitate hydratase (+191%), 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (mitochondrial) (+137%), and sphingomyelin phosphodiesterase 1, acid lysosomal (+83%), while after 24 hours there is an increase in 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (mitochondrial) (+220%), cholesterol sulfotransferase (+51%), and fatty acid transport protein (FATP) Table I Metabolism Markers Analyzed by Quantitative RT-PCR in Human Skin Explants Acyl-CoA and Acetyl-CoA synthesis • ATP citrate lyase, ACLY • acyl-CoA synthetase, FACL1 • acetyl-coenzyme A acetyltransferase 1, ACAT1 Citric acid cycle • pyruvate dehydrogenase (lipoamide) alpha 1, PDHA1 • dihydrolipoamide S-acetyltransferase, DLAT • citrate synthase, CS • aconitase 1, soluble, ACO1 • aconitase 2 mitochondrial, aconitate hydratase, ACO2 • malate dehydrogenase 1, NAD (cytosolic soluble), MDH1 • malate dehydrogenase 2, NAD (mitochondrial), MDH2 Mevalonate pathway • 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (soluble), HMGCS1 • 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (mitochondrial), HMGCS2 • 3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMGCoAred Glycoysis • glucose phosphate isomerase, GPI • glucose-6-phosphate dehydrogenase, G6PD Fatty acid beta oxidation • carnitine acetyltransferase, CRAT • acetyl-coenzyme A carboxylase alpha, ACACA Lipid synthesis • fatty acid synthase, FAS • cholesterol sulfotransferase, SULT2B1 • glucosidase, beta acid (includes glucosylceramidase), GBA • glucosylceramide synthase (ceramide glucosyltranferase), UGCG • sphingomyelin phosphodiesterase 1, acid lysosomal, SMPD1 • arachidonate lipoxygenase 3, ALOXE3 • serine palmitoyltransferase, long chain base subunit 1, SPTLC1 Lipid transport • ATP-binding cassette, sub-family A (ABC1), member 12, ABCA12 • epidermal fatty acid-binding protein 5 FABP5 • fatty acid transport protein (FATP) SLC27A4

JOURNAL OF COSMETIC SCIENCE 8 Table II Metabolism Marker mRNAs from Human Skin Explants Treated with an Emulsion Containing D-panthenyl triacetate (PTA) or D-panthenol (PAN) at 2% mRNA Marker PTA 6 h PAN 6 h PTA 24 h PAN 24 h ATP citrate lyase ACLY -56 2 20 11 Acyl-coenzyme A synthetase FACL1 12 -7 4 -1 Acetyl-coenzyme A acetyltransferase 1 ACAT1 -29 -4 3 1 Pyruvate dehydrogenase (lipoamide) alpha 1 PDHA1 -40 -10 -1 -14 Dihydrolipoamide S-acetyltransferase DLAT -52 6 11 -12 Citrate synthase CS -23 15 49 23 Aconitase 1, soluble ACO1 -16 14 25 -23 Aconitase 2 mitochondrial, aconitate hydratase ACO2 72 191 7 26 Malate dehydrogenase 1, NAD (cytosolic soluble) MDH1 34 48 -6 -6 Malate dehydrogenase 2, NAD (mitochondrial) MDH2 11 8 62 -5 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (soluble) HMGCS1 43 -61 0 -35 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (metochondrial) HMGCS2 218 137 201 220 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMG-CoAred -36 -15 8 7 Glucose phosphate isomerase GPI 14 -2 55 2 Glucose-6-phosphate dehydrogenase G6PD -25 -3 68 -14 Carnitine acetyltransferase CRAT -15 21 30 47 Acetyl-coenzyme A carboxylase alpha ACACA -50 32 4 36 Fatty acid synthase FAS -42 18 39 11 Cholesterol sulfotransferase SULT2B1 -9 7 60 51 Glucosidase, beta acid (includes glucosylceramidase) GBA -14 34 -3 6 Glucosylceramide synthase (ceramide glucosyltransferase) UGCG -20 12 33 36 Sphingomyelin phosphodiesterase 1, acid lysosomal SMPD1 -10 83 -37 -20 Arachidonate lipoxygenase 3 ALOXE3 -7 37 42 50 Serine palmitoyltransferase, long chain base subunit 1 SPTLC1 -32 -9 -4 -2 ATP-binding cassette, sub-family A (ABC1), member 12 ABCA12 -62 17 -36 18 Epidermal fatty acid-binding protein 5 FABP5 -34 -19 -65 13 Fatty acid transport protein (FATP) SLC27A4 -15 32 38 59 Differences (expressed as %) are versus a control emulsion. Treatment was for six hours or 24 hours. In bold: signifi cant differences (see text). (+59%). When these data are examined, it appears, as expected, that some of the activi- ties observed for PTA are confi rmed with PAN, in particular the push for the citric acid cycle, the mevalonate pathway, and the synthesis of cholesterol sulfate. However, we don’t detect activities regarding glycolysis, and the effect on lipid transport is mainly positive (while PTA was negative). The results from the metabolic markers indicate that PTA and PAN have common mechanisms but also differ.