1. Significance of VFA absorption
References
Church
Sjersen
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

2. Portal blood To liver & Na+ Rumen Epithelium HAc peripheral tissue H+
dependent Ac
HCO3-
CO2 H+
Na+
Epithelium
HAc
Ac-
Metabolism
(30% Ac, 50% Prop,
90% But)
Aerobic Anerobic
CO Ketones
Carbonic (Acetoacetate,
anhydrase B-(OH)-butyrate)
H2CO3
HCO Lactate H+
Na+
Transporters:
Anion exchange,
Putative anion
transport,
Downregulated
In adenoma
Proton-linked
monocarboxylate
transporter
Na+/H+ exchange
Na+/H+ exchange

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
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

4. 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

5. 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

6. VFA Metabolism References Church pp 279-290; 286-289
Ruckebusch pp
Sjersen pp ;

7. Post-absorption Uptake by the liver Butyrate 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

8. 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

9. Uses of VFAs Maintenance energy ATP CoA Net/mole
Acetate Acetyl CoA TCA cycle 12 ATP + 2CO
2ATP CoA CO2
Propionate Succinyl CoA TCA cycle 20 ATP + 4CO2 18
2ATP CoA
Butyrate Acetyl CoA TCA cycle ATP + 4CO
5 ATP

10. 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 x (7.3 x 10
/673) /209.4)
Propionate
Butyrate
Glucose
____________________________________________________________
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

11. Gluconeogenesis Glucose requirements 15 – 20% of glucose utilization
Central nervous system
15 – 20% of glucose utilization
Pregnancy
For fetus
Lactation
Lactose synthesis
Lipid synthesis
NADPH for fatty acid synthesis
Glycerol

12. Precursors for gluconeogenesis
% of Glucose from:
Precursor Fed Fasted
Propionate –
Amino acids –
(Primarily Alanine,
Glutamine, Glutamate)
Lactate
Glycerol

13. Mechanism of gluconeogenesis Controlling enzymes
Pyruvate carboxylase
(Pyr > OAA)
NAD-malate
dehydrogenase
(Mal > OAA)
PEP carboxykinase
(OAA > PEP)
Fructose-1,6-
diphosphatase
(Fru-1,6-P > Fru-6-P)
Glucose-6-phosphatase
(Glu-6-P > Glu)
Hormones
Glucagon and Glucorticoids
Insulin

14. Glucose conservation Low blood glucose
Low hexokinase activity in the liver
Little glucose used for long chain fatty acid synthesis in ruminants

15. 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

16. 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

17. 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

18. 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

19. 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 High grain
Conjugated linoleic acid Conjugated linoleic acid
(cis-9, trans-11 CLA) (trans-10, cis-12 CLA)
Vaccenic acid trans-10 C18:1
(trans-11 C18:1)
Stearic acid Stearic acid
C18: C18:0

20. 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