title: Diverse captive non-human primates with phytanic acid-deficient diets rich in plant products have substantial phytanic acid levels in their red blood cells.
abstract: BACKGROUND
  Humans and rodents with impaired phytanic acid (PA) metabolism can accumulate toxic stores of PA that have deleterious effects on multiple organ systems. Ruminants and certain fish obtain PA from the microbial degradation of dietary chlorophyll and/or through chlorophyll-derived precursors. In contrast, humans cannot derive PA from chlorophyll and instead normally obtain it only from meat, dairy, and fish products.
  
  
  RESULTS
  Captive apes and Old world monkeys had significantly higher red blood cell (RBC) PA levels relative to humans when all subjects were fed PA-deficient diets. Given the adverse health effects resulting from PA over accumulation, we investigated the molecular evolution of thirteen PA metabolism genes in apes, Old world monkeys, and New world monkeys. All non-human primate (NHP) orthologs are predicted to encode full-length proteins with the marmoset Phyh gene containing a rare, but functional, GA splice donor dinucleotide. Acox2, Scp2, and Pecr sequences had amino acid positions with accelerated substitution rates while Amacr had significant variation in evolutionary rates in apes relative to other primates.
  
  
  CONCLUSIONS
  Unlike humans, diverse captive NHPs with PA-deficient diets rich in plant products have substantial RBC PA levels. The favored hypothesis is that NHPs can derive significant amounts of PA from the degradation of ingested chlorophyll through gut fermentation. If correct, this raises the possibility that RBC PA levels could serve as a biomarker for evaluating the digestive health of captive NHPs. Furthermore, the evolutionary rates of the several genes relevant to PA metabolism provide candidate genetic adaptations to NHP diets.
authors: Department of Biochemistry and Molecular Biology, Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90089, USA.
authors: Ann B
authors: AB
authors: Moser
authors: Jody
authors: J
authors: Hey
authors: Patricia K
authors: PK
authors: Dranchak
authors: Mazen W
authors: MW
authors: Karaman
authors: Junsong
authors: J
authors: Zhao
authors: Laura A
authors: LA
authors: Cox
authors: Oliver A
authors: OA
authors: Ryder
authors: Joseph G
authors: JG
authors: Hacia
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002144:Callithrix / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002734:Chlorophyll / Q000378:metabolism*; D014676:Diet, Vegetarian; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D015186:Hominidae / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics / Q000378:metabolism; D048530:Papio anubis / Q000235:genetics / Q000378:metabolism*; D010831:Phytanic Acid / Q000378:metabolism*; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins; C072087:sterol carrier proteins; D002734:Chlorophyll; D010831:Phytanic Acid; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C434934:trans-2-enoyl-CoA reductase (NADPH); D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase
references: J Lipid Res. 1966 Sep;7(5):684-91
references: 4165840
references: Biochim Biophys Acta. 2011 Sep;1811(9):498-507
references: 21683154
references: Genome Res. 2011 Oct;21(10):1640-9
references: 21685127
references: Annu Rev Nutr. 2010 Aug 21;30:291-314
references: 20420525
references: Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17712-7
references: 19004801
references: J Lipid Res. 1968 Sep;9(5):636-41
references: 4177872
references: Q Rev Biol. 2004 Mar;79(1):3-50
references: 15101252
references: Proc Biol Sci. 2011 Apr 7;278(1708):961-9
references: 21177690
references: Cell Mol Life Sci. 2006 Aug;63(15):1752-65
references: 16799769
references: Nucleic Acids Res. 2003 Jul 1;31(13):3631-4
references: 12824382
references: BMC Physiol. 2010 Oct 08;10:19
references: 20932325
references: EMBO J. 2003 Apr 1;22(7):1620-31
references: 12660168
references: Hum Mutat. 2009 Mar;30(3):E467-80
references: 19105186
references: Lipids Health Dis. 2011 Jun 17;10:101
references: 21679470
references: Nat Biotechnol. 2011 Oct 16;29(11):1019-23
references: 22002653
references: Genome Res. 2003 Jul;13(7):1619-30
references: 12840040
references: Comp Biochem Physiol A Comp Physiol. 1983;74(1):29-31
references: 6130881
references: Nature. 2011 Oct 19;478(7369):343-8
references: 22012392
references: J Mol Biol. 2004 Jul 30;341(1):119-34
references: 15312767
references: Mol Biol Evol. 2005 Apr;22(4):1107-18
references: 15689528
references: Annu Rev Plant Physiol Plant Mol Biol. 1999 Jun;50:67-95
references: 15012204
references: Genome Res. 2012 Apr;22(4):602-10
references: 22207615