Absorption of VFA 70% of VFA absorbed from rumen-reticulum 60 to 70% of remainder absorbed from omasum Papillae are important – provide surface area Absorption from rumen is by passive diffusion Concentration in portal vein less than rumen VFA concentrations Rumen 50 - 150 mM Portal blood 1 - 2 mM Peripheral blood 0.5 - 1 mM Absorption increases at lower pH H+ + Ac- HAc Undissociated acids diffuse more readily At pH 5.7 to 6.7 both forms are present, however most is dissociated At higher pH, 1 equiv of HCO3 enters the rumen with absorption of 2 equiv of VFA

VFA Absorption Absorption of Ac- Rumen Ac- Ac- Portal HAc blood H+ Metabolism HCO3- H2O H2CO3 + CO2 CO2 Carbonic Metabolism anhydrase HAc HAc

VFA Absorption Rate of absorption: Butyrate > Propionate > Acetate Absorption greater with increasing concentrations of acids in the rumen Absorption increases at lower rumen pH Absorption greater in grain fed animals Faster fermentation – More VFA produced Lower pH Growth of papillae

Metabolism of VFA by GIT Half or more of butyrate converted to - hydroxybutyric acid in rumen epithelium. 5% of propionate converted to lactic acid by rumen epithelium. Some acetate is used as energy by tissues of gut. VFA and metabolites carried by portal vein to liver.

Tissue Metabolism VFA VFA GIT tissues Liver Body tissues Use of VFA Energy Carbon for synthesis Long-chain fatty acids Glucose Amino acids Other

Utilization of Acetate in Metabolism 1. Acetate (As energy) Energy Acetate Acetyl CoA Krebs cycle 2 CO2 2 carbons (10 ATP/mole) 2. Acetate (Carbon for synthesis of fatty acids – in adipose) Acetate Acetyl CoA Fatty acids Lipids H+NADPH NADP+ Glycerol Pentose PO4 CO2 shunt Glucose

Utilization of Butryate in Metabolism Butyrate (As energy) Butyrate Butyrl CoA B-hydroxybutyrate Acetyl CoA Krebs cycle 2 CO2 Energy (27 ATP/mole) Some butyrate also used as a primer for short-chain fatty acids

Utilization of Propionate in Metabolism Propionate Propionyl CoA Methylmalonyl CoA CO2 Succinyl CoA Vit B12 Glucose Krebs cycle 2 CO2 Energy (18 ATP/mole)

Utilization of VFA in Metabolism Summary Acetate Energy Carbon source for fatty acids Adipose Mammary gland Not used for net synthesis of glucose Propionate Precursor of glucose Butyrate Carbon source for fatty acids - mammary

Effect of VFA on Endocrine System Propionate Increases blood glucose Stimulates release of insulin Butryate Not used for synthesis of glucose Stimulates release of glucagon Acetate Does not stimulate release of insulin Glucose

Energetic Efficiency of VFA in Metabolism ATP/mole Energy in ATP % Heat of (kcal/mole) combustion Acetate 10 76.0 36.3 Propionate 18 136.8 37.2 Butyrate 27 205.2 39.1 Glucose 38 288.8 42.9

Energetic Efficiency of VFA Fermentation and Metabolism Cellulose 10 Glucose VFA ATP (6730 kcal) (5240 kcal (1946 kcal) 60A 28.9% Starch 30P 10B Absorbed as glucose ATP (6730 kcal) (2888 kcal) 42.9%

Lower Energy Value of Roughage Compared with Grain Less digested Lignin limits digestibility of digestible fiber - Greater energy lost from fermentation CH4 Heat - Increased rumination Rumen contractions Chewing - More bulk in digestive tract

Comparative Prices of Corn and Alfalfa Hay NEg Mcal/kg $/ton DM $/Mcal Corn 1.55 121.75 0.0864 Alfalfa hay 0.68 75.00 0.1213

Requirements for Glucose Ruminants 1. Nervous system Energy and source of carbon 2. Fat synthesis NADPH Glycerol 3.Pregnancy Fetal energy requirement 4. Lactation Milk sugar - lactose

Sources of Glucose Carbon Ruminants Ruminants dependent on gluconeogenesis for major portion of glucose Sources of glucose in metabolism 1. Propionate 2. Amino acids 3. Lactic acid 4. Glycerol 5. Carbohydrate digestion in intestine Absorption of glucose from intestine

Glucose Synthesis Acetate Amino acids Ketone Acetyl CoA Bodies Fatty Butyrate acids Citrate Glycerol Acetyl CoA Lactate CO2 2 CO2 Pyruvate Oxaloacetate PEP Glucose Succinate Proteins Amino acids Propionate

Conservation of Glucose Ruminants 1. Glucose not extensively used for synthesis of long-chain fatty acids in adipose of ruminants - Not clear why glucose carbon is not used Glycerol is needed for synthesis of triglycerides - Comes from glucose Acetate supplies carbon for fatty acid synthesis 2. Low hexokinase activity in the liver 3. Ruminants have low blood glucose concentrations - Low concentrations of glucose in RBC

Consequences of Inadequate Glucose in Metabolism 1. Low blood glucose 2. High blood ketones 3. High blood concentrations of long-chain fatty acids (NEFA) Causes fatty liver and/or ketosis in lactating cows and pregnancy toxemia in pregnant ewes

Pregnancy Toxemia Pregnant Ewes During the last month of pregnancy Ewes with multiple fetuses Inadequate nutrition of ewe High demands for glucose by fetuses Low blood glucose and insulin Mobilization of body fat Increase in nonesterified fatty acids in blood Increased ketone production by liver

Fatty Acid Metabolism Relation to Glucose Diet fat Adipose Diet CHOH CO2 Acetate Malonyl CoA LCFA NEFA Acetate CO2 Glycerol LCFA acyl CoA 2 CO2 Triglycerides Carnitine FA acyl carnitine inhibits CO2 (Mitochondria) Ketones

Low Blood Glucose and Insulin Increased release of nonesterified fatty acids from adipose. Less synthesis of fatty acids Reduced malonyl CoA Reduced sensitivity of carnitine palmitoyl- transferase-1 to malonyl CoA Increased transfer of fatty acids into mitochondria for oxidation Increased ketone production

Fatty Acid Oxidation FA acyl carnitine Carnitine CoA FA acyl CoA Acetyl CoA CO2 Acetoacetyl CoA Acetoacetate (Mitochondria) 3-OH butyrate

Low Milk Fat Cows fed high grain diets: Reduced milk fat percentage Early theory Low rumen pH Shift from acetate to propionate production Increased blood insulin Decrease in blood growth hormone More recent theory Increased production of trans fatty acids in the rumen Trans fatty acids reduce milk fat synthesis

Long-Chain Fatty Acid Synthesis Ruminants Synthesis is primarily in adipose or mammary gland – Limited synthesis in the liver Ruminants conserve glucose supply – Glucose not extensively used for long chain fatty acid synthesis Most of carbon is supplied by acetate Some butyrate used in mammary gland Glucose metabolism supplies some of NADPH needed for fatty acid synthesis

Long-Chain Fatty Acid Synthesis Lactic acid, Propionate, Amino acids Glucose Ruminants limit use of glucose Acetyl-CoA carboxylase Acetyl CoA Fatty acids Triglycerides NADPH NADP Acetate Glycerol-3-P Glu-6-P dehydrogenase Gly-3-P dehydrogenase Glucose

Long-Chain Fatty Acid Synthesis Glucose NADPH NADP Pyruvate Malate Fatty acids Malate dehydrogenase NADP Pyruvate Oxaloacetate NADPH Acetyl CoA Acetyl CoA Oxaloacetate Citrate lyase Citrate Citrate Acetate Mitocondria Cytosol

Long-Chain Fatty Acid Synthesis Citrate Citrate Isocitrate NADP Isocitrate NADPH dehydrogenase a-Ketoglutarate Mitochondria Cytosol Supplies about half of NADPH for fatty acid synthesis

Long-Chain Fatty Acid Synthesis Butyrate Can be used in mammary gland as primer for synthesis of fatty acids Shorter chain acids Methylmalonyl (propionate) Is used as primer for synthesis of fatty acids in sheep fed high-grain diets Branched-chain acids