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Transcript
VFA Absorption • References – Church – Sjersen 176-177 173-195 • Significance of VFA absorption – VFA production = 5 moles/kg DM – 95% of the VFA are absorbed before the abomasum – 15% of the VFA (primarily butyrate) do not enter portal circulation • VFA absorption is through diffusion and facilitated transport modified by metabolism – No active transport Rumen HAc pH dependent Ac HCO3CO2 HAc HAc AcTransporters: Anion exchange, Putative anion transport, Downregulated In adenoma Metabolism (30% Ac, 50% Prop, 90% But) Aerobic Anerobic CO2 Ketones Carbonic (Acetoacetate, anhydrase B-(OH)-butyrate) H2CO3 HCO3- H+ Na+ Portal blood Epithelium Lactate H+ Na+/H+ exchange Na+ Proton-linked monocarboxylate transporter Na+/H+ exchange To liver & peripheral tissue H+ H+ Na+ • Results of VFA absorption and metabolism – 90% of the circulating VFA is acetate – 80% of the circulating ketones is B-OH-butyrate • Some produced from metabolism of acetoacetate in the liver • Factors affecting VFA absorption – VFA concentration in rumen • 3-fold increase (no change in pH) – Increases acetate absorption 2-fold – Increases butyrate absorption 4-fold with no increase in metabolism – Chain length • At pH 7.4, Ac > Prop > But – pH • Decreased pH increases VFA absorption • From pH 7.4 to 6.4 – – – – No effect on acetate 2-fold increase in propionate 4-fold increase in butyrate Result: But > Prop > Ac • Advantages of epithelial metabolism of VFAs – Provides energy to epithelial cells • Total viscera requires 25% of the total energy requirement • Use of VFAs as an energy source spares glucose • Relatively minor use – Aerobic metabolism yields CO2 used for production of HCO3 needed for acid-base balance – Reduces concentration gradient to allow more VFA absorption – Ketone bodies can bypass liver metabolism and, thereby, provide energy to peripheral tissues and C for fatty acid synthesis – Detoxifies n-butyrate • Effects of diet on VFA absorption – Increased proportion of grain in diet • • • • Increased VFA production in rumen Decreased rumen pH Greater proportion of VFA in undissociated form Greater size of papillae, number of epithelial cells, and blood flow • Upregulation of transport proteins • Increased VFA metabolism in epithelium – Only because of increased number of epithelial cells • Increased VFA absorption by 4-fold VFA Metabolism • References – Church pp 279-290; 286-289 – Ruckebusch pp. 485-500 – Sjersen pp. 249-265; 389-409 • Post-absorption – Uptake by the liver • Acetate – Very little removed by liver – Most transported to peripheral tissues for » Oxidation » Long chain fatty acid synthesis • Propionate – 94% of propionate entering liver is metabolized – Use » Gluconeogenisis • Butyrate – Liver has low affinity for B-OH-butyrate – Approx 20% of butyrate in rumen is metabolized in the liver » Acetoacetate > B-OH-butyrate – Uses » Oxidation » Long chain fatty acid synthesis – Control of location of VFA metabolism • Location of specific acyl-CoA synthetases – Acetate » Acetyl CoA synthetase High in peripheral tissues Low in rumen epithelium and liver – Propionate » Propionyl CoA synthetase Low in rumen epithelium High in liver – Butyrate » Butyryl CoA synthetase High in rumen epithelium Present in heart muscle May also be activitated by medium chain fatty acid-CoA synthetase in peripheral tissues • Uses of VFAs – Maintenance energy ATP CoA Acetate Acetyl CoA Net/mole TCA cycle 12 ATP + 2CO2 10 2ATP CoA CO2 Propionate Succinyl CoA TCA cycle 20 ATP + 4CO2 18 2ATP CoA Butyrate Acetyl CoA 5 ATP TCA cycle 24 ATP + 4CO2 27 – Efficiency of VFAs for energy metabolism Mole ATP Heat of Mole acid Efficiency /mole Efficiency combustion produced of acid of VFA kcal/mole /glucose Fermentation oxidized combustion Acetate 209.4 2 62.2 10 34.8 (209.4 x 2 (7.3 x 10 /673) /209.4) Propionate 367.2 2 109.1 18 35.8 Butyrate 524.3 1 77.9 27 37.6 Glucose 673 38 41.2 ____________________________________________________________ • Implications – Little difference in efficiency of use of Acetate, Propionate and Butyrate over a wide range of concentrations – Balance is required between VFAs for efficient use – Difference in total efficiency between different fermentation types is associated with the efficiency of fermentation – Gluconeogenesis • Glucose requirements – Central nervous system » 15 – 20% of glucose utilization – Pregnancy » For fetus – Lactation » Lactose synthesis – Lipid synthesis » NADPH for fatty acid synthesis » Glycerol – Precursors for gluconeogenesis Precursor Propionate Amino acids (Primarily Alanine, Glutamine, Glutamate) Lactate Glycerol % of Glucose from: Fed Fasted 40 – 60 0 15 – 30 35 15 5 40 25 – Mechanism of gluconeogenesis – Controlling enzymes • Pyruvate carboxylase (Pyr > OAA) • NAD-malate dehydrogenase (Mal > OAA) • PEP carboxykinase (OAA > PEP) • Fructose-1,6diphosphatase (Fru-1,6-P > Fru-6-P) • Glucose-6-phosphatase (Glu-6-P > Glu) – Hormones • Glucagon and Glucorticoids • Insulin – Glucose conservation • Low blood glucose • Low hexokinase activity in the liver • Little glucose used for long chain fatty acid synthesis in ruminants – Fatty acid synthesis • Locations – Nonlactating animals » 92% of fatty acid synthesis is in adipose tissue and 6% is in the liver – Lactating animals » 40% of fatty acids in milk fat are synthesized in mammary gland • Why glucose is not a Csource for fatty acid synthesis – Limiting enzymes – Bauman Citrate lyase Malate dehydrogenase – Baldwin Pyruvate kinase Pyruvate dehydrogenase – Use of glucose for fat synthesis • Supply NADPH • Synthesis of glycerol – Precursors for fatty acid synthesis in ruminants • Acetate – 75 – 90% of C in C4 – C14 fatty acids – 20% of C in palmitate (C16) – 0% of C in C18 • Butyrate – Acetate and B(OH)butyrate contribute equally to the first 4 carbons – Must be converted to acetyl CoA for additional C • Lactate – 5 – 10% of the fatty acids in milk – Inversely related to the amount of acetate available » Controlled by pyruvate dehydrogenase – Additional uses of lactate » Glycerol » NADPH from Isocitrate cycle • Propionate – Precursor for odd and branched chain fatty acids – Increased by increased concentration of methylmalonyl CoA from vitamin B12 deficiency • Energy partitioning between adipose and milk fat – High grain diets with deficient eNDF will result in reduction in milk fat synthesis and increase adipose tissue – Insulin-glucogenic theory • • • • Increases propionate and reduces acetate production Increases glucose synthesis Increases insulin secretion Increases glucose uptake by adipose tissue, but not mammary gland • Increases NADPH synthesis in adipose tissue • Increases fatty acid synthesis in adipose tissue, making less acetate available for mammary gland • Now believed that insulin plays a minor role in milk fat depression – Biohydrogenation theory • High grain diets, diets with deficient eNDF, or diets high in polyunsaturated fatty acids – Increase production of trans-10, cis-12 conjugated linoleic acid (CLA) Linoleic acid (cis-9, cis-12 C18:2) High forage Conjugated linoleic acid (cis-9, trans-11 CLA) High grain Conjugated linoleic acid (trans-10, cis-12 CLA) Vaccenic acid (trans-11 C18:1) trans-10 C18:1 Stearic acid C18:0 Stearic acid C18:0 – Even at low doses (<5 g/d), trans-10, cis-12 CLA inhibits fat synthesis in mammary gland • Mechanism – trans-10, cis-12 CLA inhibits migration of Sterol Response Element-Binding Protein (SREBP) transcriptional factor to the nucleus of mammary cells – Results in reduction in mRNA for genes involved in: » Fatty acid uptake Lipoprotein lipase » Fatty acid transport Fatty acid binding protein » Fatty acid synthesis Acetyl CoA carboxylase Fatty acid synthase » Fatty acid desaturation Stearoyl-CoA desaturase » Triglyceride synthesis Acylglycerol phosphate acyl transferase Glycerol phosphate acyl transferase