VFA Absorption and Metabolism

1
VFA Absorption and Metabolism

• References
• Church
• Absorption of VFA from the Reticulo-rumen, pp.
  176-177
• VFA absorption and metabolism, pp. 279-280
• Gluconeogenesis, pp 286-290

2

• VFA absorption

• Significance of VFA absorption
• 95 of the VFA are absorbed before the abomasum
• 15 of the VFA (primarily butyrate) entering
  rumen epithelium do not enter portal circulation
• VFA absorption is through diffusion and
  facilitated transport modified by metabolism
• No active transport
• VFA metabolism in the ruminal epithelium
• Acetate
• None
• Propionate
• Approximately 50 converted to lactate
• Butyrate
• Approximately 90 converted to ketones
  (Beta-OH-butyrate or acetoacetate)

3

• 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
• Increases VFA absorption
• Effect largest on butyrate
• Chain length
• At pH 7.4, Ac gt Prop gt But
• pH
• Decreased pH increases VFA absorption
• Effect largest on butyrate

4

• Effects of diet on VFA absorption
• Increased proportion of grain in diet
• Increased VFA production and concentration in
  rumen
• Decreased rumen pH
• Increased VFA metabolism in the epithelium
• Greater size of papillae, number of epithelial
  cells, and blood flow
• Upregulation of transport proteins
• Increased VFA absorption
• Increases insulin secretion
• Increases blood flow
• Results in increased growth of rumen papillae
• Excessive butyrate absorption
• Inhibits epithelial mitosis
• Results in parakeratosis

5

• Post-absorption metabolism of VFA
• 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
• Gluconeogenesis
• Butyrate
• Liver has low affinity for B-OH-butyrate
• Approx 20 of butyrate in rumen is metabolized in
  the liver
• Acetoacetate gt B-OH-butyrate
• Uses
• Oxidation
• Long chain fatty acid synthesis

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• Uses of VFAs
• Maintenance energy
• ATP CoA
  Net/mole
  
  
• Acetate Acetyl CoA TCA cycle
  12 ATP 2CO2 10
• 2ATP CoA CO2
• Propionate Succinyl CoA TCA cycle
  20 ATP 4CO2 18
• 2ATP CoA
• Butyrate Acetyl CoA TCA cycle
  24 ATP 4CO2 27
• 5 ATP

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• 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

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• Efficiency of VFA use of maintenance
• Energy spared from fat
• 
  and protein oxidation/
• VFA Molar proportions Energy supplied
  from VFA,
• Ac 100 59.2
• Prop 100 86.5
• But 100 76.4
• PropBut 6040 90.7
• AcPropBut 254530 87.2
• AcPropBut 503020 83.1
• AcPropBut 751510 85.6
• AcPropBut 9064 84.7
• AcBut 9010 65.0

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• 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

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• Precursors for gluconeogenesis
• 
  of Glucose from
• Precursor Fed
  Fasted
• Propionate 40 60
  0
• Amino acids 15 30
  35
• (Primarily Alanine,
• Glutamine, Glutamate)
• Lactate 15
  40
• Glycerol 5
  25

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• Mechanism of gluconeogenesis
• Hormones
• Glucagon and
• Glucorticoids stimulates
• Insulin inhibits

From Van Soest, 1994
12

• Glucose conservation
• Low blood glucose
• Low hexokinase activity in the liver
• No glucose used to supply carbon for long chain
  fatty acid synthesis in ruminants

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• 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

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• Why glucose is not a C-source 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

15

• 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

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• Energy partitioning between adipose and milk fat
• High grain diets with deficient inadequate fiber
  will result in reduction in milk fat synthesis
  and increase adipose tissue
• Insulin-glucogenic theory
• High grain diet
• 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

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• Biohydrogenation theory
• High grain diets, diets with deficient fiber, or
  diets high in polyunsaturated fatty acids
• Increase production of trans-10, cis-12
  conjugated linoleic acid (CLA)
• Linoleic acid
• (cis-9, cis-12 C182)
• High forage
  High grain
• Conjugated linoleic acid Conjugated
  linoleic acid
• (cis-9, trans-11 CLA) (trans-10,
  cis-12 CLA)
• Vaccenic acid
  trans-10 C181
• (trans-11 C181)
• Stearic acid
  Stearic acid
• C180
  C180

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• Even at low doses (lt5 g/d), trans-10, cis-12 CLA
  inhibits fat synthesis in mammary gland