It would be like seeing the Mona Lisa pulled down from the wall of the Louvre, wrapped in brown paper, and carted away. Or Botticelli's Birth of Venus being sold from its position at the heart of the Uffizi in Florence.

That is how dramatic the loss of the 27-strong collection of art belonging to the Duke of Sutherland would be to the National Galleries of Scotland (NGS) should they fail to raise £50m by the end of the year.

The heart of this country's national art collection - visited by tens of thousands of visitors every year, its paintings an inspiration to generations of Scots, visitors, and artists - would be lost forever, sold to the highest bidders on the open market.

"It would be a catastrophe," said Nicholas Penny, the director of the National Gallery in London, yesterday, "not only for Scotland - for the whole of the UK".

The comparisons to the most famous treasures of the Louvre and the Uffizi were made yesterday by John Leighton, the director general of the NGS, as years of speculation over the future of the paintings in the Bridgewater Collection - the official title of the masterpieces owned by the 7th Duke of Sutherland, and loaned for many years to the NGS - came to a dramatic head.

"We have known," he said, "for decades that a moment like this would arrive, and when you see the values reached at auction for work like this, it was inevitable.

"You could say the timing is not ideal, in light of the economic climate. But I think this is a defining moment for the National Galleries of Scotland.

"This will be the most important acquisition for some time, and a defining moment for heritage of visual arts in this country."

The retention of the Bridgewater Collection - which contains three works by Raphael, four by Titian, the most famous Rembrandt self-portrait and Poussin's revered Seven Sacraments - is the biggest challenge Mr Leighton has faced at the NGS since he took over from Sir Timothy Clifford, and, indeed, the biggest the NGS has faced since the end of the Second World War.

Art experts are united in their admiration for the paintings. They say Edinburgh's National Galleries would be permanently relegated to the also-rans of the art world if they were lost. Mr Leighton said the NGS would be reduced from a "must see" gallery to something considerably less vital.

One leading Scottish artist, John Bellany, said: "I used to study them every week. Even now, I go and stand in front of each of them for half an hour and my knees turn to jelly. They are, quite simply, superlative masterpieces. The Edinburgh and London National Galleries shouldn't hesitate in trying to acquire them, and I wish them all the best in this great enterprise."

Last year, the 7th Duke of Sutherland, Francis Egerton, decided to sell all, or some, of the paintings. Prices being reached at auction houses across the world were spiralling, and continue to do so: Roman Abramovich, the Russian billionaire, recently bought Francis Bacon's Triptych for £43m.

An arts market journal has estimated that the entire Bridgewater Collection could fetch as much as £1bn at auction, a staggering sum but one that is "very conservative", according to one senior source at the NGS.

The duke's decision to sell led to months of "cordial" behind-the-scenes bargaining and discussions. The duke may want to sell, but he is also "passionate" that they are sold to Scotland's national galleries.

In the galleries' view, in fact, the duke has made several concessions, so that could improve the chances of the paintings staying in situ: the £50m price tags are far less than the individual works would reach at auction, and the payments are to be staggered over a number of months.

A compromise, in the form of this proposed deal, has been reached: if the NGS, and its counterpart in London, come up, by December 31 this year, with £50m for one of Titian's masterpieces, Diana and Actaeon, and, four years later, another £50m for its counterpart, Diana and Callisto, the entire collection will be allowed to stay on loan at the NGS for another generation.

Yesterday a spokesman for the duke said: "The duke would very much want these pictures to continue to be accessible to public view, and to achieve this is prepared to dispose of them at a price below market value and on other terms favourable to the nation.

"He would also wish for the rest of the collection to remain on public display and the intention is that an agreement will be put in place to extend the loan for another 21 years."

But the fact remains: the NGS and, working in partnership, the National Gallery in London, now has to raise the first £50m in four months, or the whole collection is in danger of being lost to the public.

Mr Leighton said: "It could be seen as a crisis, yes, but I prefer to see it as an opportunity."

The collection of paintings was formed by Francis Egerton, the 3rd, and last, Duke of Bridgewater, who acquired them from the dispersal of the Orleans Collection after the French Revolution in 1792.

The duke had no children and on his death his estate passed to the descendants of his sister, Louisa, who had married the father of the 1st Duke of Sutherland.

In turn they passed to his youngest son, also Francis. They became the first privately-owned Old Masters on display to the public in Britain - his family put them on show in a London townhouse as early as 1806.

The collection eventually passed to the 6th Duke of Sutherland, who in 1945 placed them in the care of the National Galleries of Scotland.

Since then, the glories of the collection - Mr Penny says the two Titians are "the greatest paintings in private hands in the world" - have been on continuous public view.

Incrementally, the Bridgewater Collection has passed into public hands: there were originally 32 pieces in its portfolio - in 1984 the NGS bought four pieces by Lotto, Tintoretto, Dou and Steen.

Most recently, following the death of the 6th duke in 2000, the NGS bought Titian's Venus Anadyomene for just over £11m.

Now the biggest purchases yet from the collection will need to be made if the entire group is to remain in public hands.

"It is a big, big challenge," Mr Penny said, "and it is not going to be easy."

Duke of Sutherland, Earl of Ellesmere