Table 2.
One-carbon metabolism genes, proteins, and enzyme activities during late pregnancy and lactation in dairy cows. ↑ = gene/protein abundance and enzyme activity increase; ↓ = gene/protein abundance and enzyme activity decrease
| Stage | Dietary manipulationa | Tissue/Cellsb | Effect on abundance of gene and protein, and enzyme activityc | Reference |
|---|---|---|---|---|
| Transition period | RP-Met supply from − 28 d to 30 d relative to calving | Mammary |
↑ GCLC, GCLM, GSR, GPX1, ME1, FECH, FTH1, NQO1 gene abundance with RP-Met ↑ NFE2L2, NFKB1, MAPK14 gene abundance with RP-Met ↑ NFE2L2 activation with RP-Met |
[86] |
| RP-Met supply from −28 to 30 d relative to calving | Adipose |
↑ CBS, GCLC, GSR, and GPX1 gene abundance with RP-Met ↑ GPX1, GPX3, GSTM1, and GSTA4 protein abundance with RP-Met Activation of the GSH metabolism |
[87] | |
| RP-Met supply from −28 to 30 d relative to calving | Adipose |
↑ AA transporter gene abundance with RP-Met ↑ AKT1, RPS6KB1, and EIF4EBP1 gene abundance with RP-Met ↑ Phosphorylated AKT, PPARG and fatty acid synthase protein abundance with RP-Met ↑ mTOR protein abundance (at 30 d in milk) with RP-Met |
[88] | |
| Met supply (RP-Met or Met-analogue) from − 21 to 30 d relative to calving | Liver |
↑ SAHH, MAT1A (at 21 d in milk), CBS, MTR, and DNMT3A gene abundance with Met ↓ GSS, GCLC, and SOD1 gene abundance with Met |
[27, 89] | |
| RP-Met or Chol supply from − 21 to 30 d relative to calving | Liver | ↓ MTR enzyme activity | [27] | |
| RP-Met supply from −28 to 30 d relative to calving | Liver |
↑ CBS enzyme activity ↑ MAT1A gene abundance |
[28] | |
| Pre-partum treatment: 2 BCS categories allowed to 2 levels of energy intake (75% or 125%) in a 2 × 2 factorial design with grazing dairy cows | Liver |
↓ MTR and CBS enzyme activity postpartum ↑ BHMT enzyme activity at 7 d in milk ↑ MTR enzyme activity in thin cows ↑ CBS enzyme activity in cows at 125% energy and in thin cows at 125% energy |
[64] | |
| RP-Met or Chol supply from −21 to 30 d relative to calving | PMNL | ↓CBS, CTH, GSS, and GPX1 gene abundance | [90] | |
| RP-Met supply to prepartum high energy diet from −21 to 30 d relative to calving | PMNL |
↓ GPX1 gene abundance at −10 d from calving in cows receiving RP-Met at high energy diet ↑ GSR gene abundance in the post-partum with high energy diet ↑SAHH gene abundance in the postpartum with Met supply at high energy compared with low energy |
[91] | |
| Mid lactation | In vitro Met (40 μmol/L) or Chol (80 mg/dL) supply | PHEP |
↑ MAT1A, PEMT, SAHH, BHMT, CSAD, GCLC, and GSR abundance with Met ↑MTR, BADH, CHDH abundance with Met or Chol Greatest CHDH abundance with Chol ↑ CBS protein abundance with Met |
[35] |
| In vitro Met (Lys:Met ratio of 3.6:1, 2.9:1, or 2.4:1) and Chol (0, 400, or 800 μg/mL) supply | PMNL |
↑ CSAD, CTH, GSS, and GSR gene abundance with Chol ↑GSS and GSR gene abundance with Met at Lys:Met ratio of 2.4:1and Chol supply at 400 μg/mL |
[19] | |
| In vitro Met (Lys:Met ratio of 3.6:1, 2.9:1, or 2.4:1) with or without LPS challenge | PMNL | ↓ GSR gene abundance overall with LPS and Met (relevant effect of LPS) | [92] | |
| In vitro Met (Lys:Met ratio of 3.6:1, 2.9:1, or 2.4:1) or Chol (0, 400, or 800 μg/mL) supply under thermoneutral or heat stress conditions | PMNL |
↑ mRNA fold-change in abundance of CBS, CSAD, GSS, GSR, GPX1, TLR2, TLR4, IRAK1, IL-1β, IL-10, BAX, BCL2 and HSP70 with Chol ↓ mRNA fold-change abundance of SAHH and linear ↑ in MPO, NF-κB, and SOD1, CDO1, BAX and HSP70 with increasing Met supply |
[93] | |
| Cell culture | In vitro Met (Lys:Met ratio of 2.9:1, 2.5:1, or 2.0:1) | MAC-T |
↑ Intracellular non-essential and essential AA with Met at Lys:Met ratio of 2.0:1 ↑ β-casein and AA transporter gene abundance with Met at Lys:Met ratio of 2.9:1 ↑ mTOR activation with Met at Lys:Met ratio of 2.9:1 |
[94] |
| In vitro Met and Arg (Lys:Met 2.9:1 and Lys:Arg 2:1; Lys:Met 2.5:1; Lys:Arg 1:1 or Lys:Met 2.5:1 and Lys:Arg 1:1) | BMEC |
↑ AA transporter SLC7A1 gene abundance with Met at Lys:Met ratio of 2.5:1 ↓ AA transporters gene abundance with Arg at Lys:Arg 1:1 |
[95] |
aRP rumen-protected, Met methionine, Chol choline, Lys lysine, Arg arginine
bPMNL polymorphonuclear leukocytes cells, PHEP primary liver cells enriched with hepatocytes, MAC-T immortalized bovine mammary epithelial cell line, BMEC primary bovine mammary epithelial cells
cAA amino acids, AKT1 AKT serine/threonine kinase 1, BADH betaine aldehyde dehydrogenase, BHMT betaine homocysteine methyltransferase, BAX BCL2 associated X, apoptosis regulator, CBS cystathionine β-synthase, CDO cysteine dioxygenase, CHDH choline dehydrogenase, CSAD cysteine sulfinic acid decarboxylase, CTH cystathionine-γ-lyase, DNMT1 DNA (cytosine-5)-methyltransferase 1, DNMT3A DNA (cytosine-5)-methyltransferase 3 α, DNMT3B DNA (cytosine-5)-methyltransferase 3 β, EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1, FECH ferrochelatase, FRAP Ferric-reducing ability of plasma, FTH1 ferritin heavy chain 1, GCLC glutamate-cysteine ligase catalytic subunit, GCLM glutamate-cysteine ligase modifier subunit, GNMT glycine N-methyltransferase, GPX1 glutathione peroxidase 1, GPX3 glutathione peroxidase 3, GSR glutathione reductase, GSS glutathione synthase, GSTA4 glutathione S-transferase Alpha 4, GSTM1 glutathione S-transferase Mu 1, HSP70 heat shock protein 70, IL-1β interleukin 1-β, IL-6 interleukin 6, IL-10 interleukin 10, MAPK14 mitogen-activated protein kinase 14, MAT methionine adenosyltransferase, MAT1A methionine adenosyltransferase 1A, ME1 malic enzyme 1, MPO myeloperoxidase, mTOR mechanistic target of rapamycin, MTR 5-methyltetrahyrdofolate-homocysteine methyltransferase, NFE2L2 nuclear factor erythroid 2-like 2, NFKB1 nuclear factor κβ subunit 1, NQO1 NAD(P)H quinone dehydrogenase 1, ORAC oxygen radical absorbance capacity, PEMT phosphatidylethanolamine methyltransferase, PON paraoxanase, PPARG peroxisome proliferator activated receptor gamma, ROM reactive oxygen metabolites, RPS6KB1 ribosomal protein S6 kinase B1, SAA serum amyloid A, SAHH S-adenosylhomocysteine hydrolase, SOD1 superoxide dismutase 1