title: Control of fibrinogen biosynthesis: role of the FFA/albumin ratio.
abstract: The rate of biosynthesis and turnover of the plasma protein fibrinogen is a marker of metabolic signaling in aging and disease. The rate in the young normal human subject of 0.260 mg/ml/24 h increases to 0.378 in older normal subjects and to 0.466 in age matched coronary thrombosis patients measured by endogenous labeling of fibrinogen with L: -glutamic acid-C14. The increased rate of fibrinogen turnover has been traced to generation of fibrin by labeling the polymers with glycine C14 ethyl esters in the presence of activated fibrin stabilizing factor. Circulating fibrin increased 520% above normal in ischemic thrombotic cerebrovascular disease. Long chain saturated free fatty acids (FFA) exercise not only primary control over incorporation of Cl4 labeled amino acids into the fibrinogen structure but also activate the cascade sequence of reactions which convert fibrinogen into occlusive fibrin polymers. FFA are normally bound and transported by plasma albumin to mitochondrial sites of energy metabolism. Albumin synthesis declines with aging. This decline is associated with increased plasma levels of FFA resulting in an increase in the plasma FFA/albumin ratio. Correction of this ratio in vitro by restoration of a normal FFA/albumin ratio restores a normal level of fibrinogen synthesis by human hepatocytes.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA. eric.farr@springer.com
authors.forename: Laurence
authors.initials: L
authors.lastname: Pilgeram
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D005230:Fatty Acids, Nonesterified; D012709:Serum Albumin; D005340:Fibrinogen
references.citation: J Biol Chem. 1960 Sep;235:2595-9
references.pmid: 13817286
references.citation: Naturwissenschaften. 1993 Dec;80(12):547-55
references.pmid: 8302368
references.citation: Circulation. 1991 Mar;83(3):836-44
references.pmid: 1999035
references.citation: Arterioscler Thromb. 1994 Jan;14(1):54-9
references.pmid: 8274478
references.citation: J Pathol Bacteriol. 1946 Apr;58:207-12
references.pmid: 20996420
references.citation: Thromb Diath Haemorrh. 1963 Jul 15;143:346-53
references.pmid: 14081258
references.citation: Lancet. 1986 Sep 6;2(8506):533-7
references.pmid: 2875280
references.citation: J R Coll Gen Pract. 1985 Dec;35(281):565-9
references.pmid: 4093900
references.citation: J Appl Physiol. 1961 Jul;16:660-4
references.pmid: 13735726
references.citation: Thromb Diath Haemorrh. 1968 Nov 15;20(1):31-43
references.pmid: 5708898
references.citation: Arterioscler Thromb Vasc Biol. 1995 Sep;15(9):1263-8
references.pmid: 7670937
references.citation: J Atheroscler Res. 1968 Jan-Feb;8(1):155-66
references.pmid: 5642099
references.citation: Stroke. 1973 Jul-Aug;4(4):643-57
references.pmid: 4723694
references.citation: Arch Biochem Biophys. 1957 Oct;71(2):346-51
references.pmid: 13471036
references.citation: J Gerontol. 1958 Jan;13(1):32-42
references.pmid: 13514035
references.citation: Thromb Diath Haemorrh. 1967 May 31;17(3-4):358-64
references.pmid: 5589295
references.citation: J Clin Invest. 1963 Jun;42:860-6
references.pmid: 14022629
references.citation: Arterioscler Thromb Vasc Biol. 1996 Mar;16(3):351-6
references.pmid: 8630658
references.citation: Naturwissenschaften. 1984 Jul;71(7):372-4
references.pmid: 6482979
references.citation: Arterioscler Thromb Vasc Biol. 1995 Sep;15(9):1269-79
references.pmid: 7670938
references.citation: Am J Pathol. 1963 Dec;43:987-98
references.pmid: 14099459
references.citation: JAMA. 1987 Sep 4;258(9):1183-6
references.pmid: 3626001
references.citation: Eur Heart J. 1992 Feb;13(2):166-70
references.pmid: 1313369
references.citation: J Atheroscler Res. 1964 May-Jun;4:244-53
references.pmid: 14181607
references.citation: Circulation. 1997 Dec 16;96(12):4204-10
references.pmid: 9416883
references.citation: Lancet. 1949 Nov 19;2(6586):925-7
references.pmid: 15395606