8 mole of glucose. Propionic acid is produced via 2 main pathways: 1 fixation of CO
2
to form succinate the dicarboxylic pathway; and 2 from lactate and acrylate. Pyruvate is an intermediate compound
for SCFA production, then can be metabolized to acetate, butyrate, and propionate.
2.5 BENEFICIAL OF SHORT CHAIN FATTY ACID ON COLON
CANCER
Short chain fatty acid is an organic fatty acid with 1 to 6 carbon atoms. It is the principal anion which arised from bacterial fermentation of polysaccharide, oligosaccharide, proteins, peptide,
and glycoprotein precursors in the colon Cumming et al, 1997. Production of SCFA is affected by many factors, including numbers and types of microflora present in the colon Roberfroid, 2005,
substrate source Cook and Sellin 1998, gut transit time, hexose availability, enzyme production of bacteria, and amount of carbohydrate. Various population data showed that SCFA production in order
of acetate:propionate:butyrate in a molar ration of approximately 60:20:20 or 3:1:1, respectively in the proximal and distal colon Topping and Clifton, 2001
Short chain fatty acids, the major by-product of fermentation, have several actions that appear relevant to maintaining the health of the large bowel. They are rapidly absorbed by the colonic
mucosa, promoting water and sodium absorption, and thereby preventing osmotic diarrhea Ruppin et al, 1980. Also, together with lactate, they help to acidify the colonic lumen Macfarlene et al, 1991.
A low pH reduces the bacterial conversion of primary bile acids into secondary bile acids Cummings, 1983. In addition, a low pH can affect other processes including the ionization of SCFA; epithelial
proliferation; the balance of bacterial species; bacterial metabolism of ingested carcinogens; bacterial activation of oxygen free radicals; the activity of bacterial enzymes e.g.
β-glucosidase, β- glucuronidase; and faecal water cytotoxicity Cummings, 1983.
Acetate or acetic acid C
2
H
4
O
2
is an organic acid which is colorless and gives vinegar sour taste. Acetate is an essential metabolic fuel in ruminant animal because all glucose reaching the rumen
is fermented by the resident bacteria Cummings, 1997. Acetate is rapidly cleared from the blood with a half life of only a few minutes Skutches et al, 1979 and is metabolized by skeletal and cardiac
muscle Scheppach et al, 1991. Acetate either orally or intravenously has little effect on glucose metabolism and does not stimulate insulin release in man Scheppach et al, 1988
Propionate or propionic acid CH
3
CH
2
COOH is a clear, colorless liquid with a slightly sweetish odor. Propionate can be found in portal blood, although some may be metabolized in the
colonic epithelium and may be a differentiating factor, but with less power than butyrate Gamet et al, 1992. Some experiment have shown inhibition of hepatic cholesterol synthesis by propionate and
redistribution of cholesterol from plasma to liver Chen et al, 1984 There is strong evidence that short chain fatty acid butyrate is important for the metabolic
welfare of the epithelium of the large bowel. Butyrate is utilized as an important energy source by the colonocyte, the main cell type in the colon Roediger, 1982. Butyrate also has a range of effects
particularly relevant to bowel cancer. It ‘stabilizes’ DNA by inhibiting histone deacetylase Candido et al, 1978 and increasing methylation of DNA; it induces differentiation; and it reduces the growth
rate in a range of mammalian cells, including colorectal cancer cell lines Whitehead, 1987. Recent interest has also focused on the effects of butyrate on induction of apoptosis i.e. programmed cell
death of colonic epithelial cells Hague et al, 1993.
CHAPTER III METHODOLOGY
