William Hill and Ladbrokes estimated 150 million pounds ($224.09 million) will wagered on the Aintree steeplechase, much of that from once-a-year punters, with up to a third of that on McCoy.
"The total cost for the industry if he wins - 30 million - would be the worst Grand National result ever," said Ladbrokes' Alex Donohue.
If the Northern Irishman wins it will almost certainly be his last ride in a record-breaking career that will see him crowned champion jockey for the 20th successive season this month.
He has captured the headlines, the public imagination and the money.
"We are all poised for a big betting wave on Shutthefrontdoor," said William Hill's Jon Ivan-Duke.
"It would be tens of millions paid out if he were to win. I think it could be potentially the worst result of the year for bookmakers in terms of the payout."
The last favourite to win the National was trainer Jonjo O'Neill and owner JP McManus's Don't Push it in 2010, with McCoy in the saddle for an emotional first triumph after 15 failed attempts.
Shutthefrontdoor, also trained by O'Neill and winner of the 2014 Irish Grand National, is currently 7/1 but the eight-year-old could halve to 7/2, making the shortest-priced favourite since Red Rum in 1975.
"AP McCoy is the only story in town as far as those having a once a year flutter are concerned," said Donohue.
However, the National has always been a lottery, ever since a horse of that name won in 1839, and there will be 39 other runners.
"People choose their Grand National horses in a unique way we don't usually see on any other betting race of the year," said Ivan-Duke.
"Quite regularly we'll find a horse that we don't expect to be well-backed that people just like the name of. Shakalakaboomboom was quite well backed last year."
Hill's expected to take five million bets on the race and turn over 30 million pounds on Saturday. Some 10,000 bets a minute will be placed on online and mobile platforms alone at the peak.
"There will be something approaching 20,000 bets a minute in the final few minutes before the start," said Ivan-Duke.
(Reporting by Alan Baldwin, editing by Justin Palmer)
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