* Assad whereabouts unknown, rebels close net on capital
* Fighting rages as night falls and army shells Damascus
* Defence minister, Assad brother-in-law, top general killed
(Adds new reports of fighting, Ban Ki-moon comments)
By Mariam Karouny and Oliver Holmes
BEIRUT, July 19 (Reuters) - Mystery surrounded the whereabouts of Syrian President Bashar al-Assad on Thursday, as battles raged in the centre of Damascus a day after a bomber killed his top security chiefs.
The Syrian leader made no public appearance and no statement after a bomb in the heart of the capital killed his powerful brother-in-law, his defence minister and a top general, drawing fierce army retaliation with heavy artillery against the rebels.
On Thursday morning, residents said there was no let-up in the heaviest fighting to hit the city in a 16-month revolt against Assad's rule, now into its fifth day.
The fighting came within sight of the presidential palace, near the security headquarters where the bomber struck a crisis meeting of defence and security chiefs.
Residents in the Midan and Kafr Souseh districts said they heard explosions and heavy gunfire as helicopters buzzed overhead.
Checkpoints around Midan and the ancient walled Old City of Damascus had been removed, they said. It was unclear if security forces had changed tactics to prevent rebels from targeting soldiers, or if it was a temporary move in the heat of battle.
On Wednesday, an explosion which nearly no residents heard struck at the heart of Assad's government. Following the attack, rebellious neighbourhoods were plunged into fierce battles.
Assad's brother-in-law Assef Shawkat, a top commander and one of the pillars of the Assad clan's rule, was killed in the Wednesday blast along with Defence Minister Daoud Rajha.
Another senior general was also killed and the heads of intelligence and the Interior Ministry were wounded, deeply damaging the security apparatus of the Assad family, which has ruled the country with an iron fist for four decades.
The army shelled its own capital from the surrounding mountains as night fell on Wednesday. Government troops, having vowed retaliation for the assassination, fired machineguns into the city from helicopters.
Rebels, massed in several neighbourhoods, are armed mostly with small arms and rocket-propelled grenades.
Activist videos posted on the Internet showed bloodied bodies lying in the street.
Local media, citing security sources, said Assad was still in the capital but gave no further details.
FEARS OF DESTABILISATION
A security source said the bomber who struck inside the security headquarters was a bodyguard for Assad's inner circle. Anti-Assad groups claimed responsibility.
U.N. Secretary-General Ban Ki-moon condemned the Damascus blast and expressed grave concern over the use of heavy weapons.
"Time is of the essence," he said. "The Syrian people have suffered for too long. The bloodshed must end now."
The U.N. Security Council put off a scheduled vote on a Syria resolution until Thursday and U.S. President Barack Obama telephoned President Vladimir Putin of Russia, Assad's main ally, to try to persuade Moscow to drop support for him.
Western leaders fear the conflict, which has been joined by al Qaeda-style jihadists, could destabilise Syria's neighbours: Israel, Lebanon, Turkey, Iraq and Jordan.
U.S. Defence Secretary Leon Panetta said: "This is a situation that is rapidly spinning out of control." He called for maximum global pressure on Assad to step down.
Russian Foreign Minister Sergei Lavrov said "the decisive fight" was under way in Damascus.
British Prime Minister David Cameron, whose government has sponsored the sanctions resolution, said on Thursday it was time for Assad to go to avoid an all-out civil war.
The generals killed and wounded in the bombing form the core of Assad's crisis unit to crush the revolt, which grew out of protests inspired by Arab Spring uprisings that unseated leaders in Tunisia, Egypt and Libya.
The armed forces chief of staff, Fahad Jassim al-Freij, quickly took over as defence minister, avoiding any impression of official paralysis.
"This cowardly terrorist act will not deter our men in the armed forces from continuing their sacred mission of pursuing the remnants of these armed terrorist criminal gangs," Freij said on state television. "They will cut off every hand that tries to hurt the security of the nation or its citizens."
The bombing appeared to be part of a coordinated assault on the capital that has escalated since the start of the week. Rebel fighters call it the "liberation of Damascus" after months of fierce clashes which activists say have killed 17,000 people.
Neighbouring Jordan's King Abdullah said violence may have ruled out the possibility of a negotiated power transition.
"The realities on the ground may have overtaken us, therefore I think the clock is ticking and we have... reached the point where the political option is too late," he told CNN in an interview.
Rebels were jubilant at their success in penetrating into the capital. Abdullah al-Shami, a rebel commander based in Turkey, said: "I expect a speedy collapse of the regime ... and it means we will not be in need of outside intervention, with the regime beginning to crumble much faster than we envisaged."
Yet some opposition figures said victory would still not be easy.
"It is going to be difficult to sustain supply lines and the rebels may have to make a tactical withdrawal at one point, like they did in other cities," veteran opposition activist Fawaz Tello said from Istanbul.
"But what is clear is that Damascus has joined the revolt."
(Additional reporting by Erika Solomon and Dominic Evans in Beirut, Khaled Yacoub Oweis in Amman, Suleiman Al-Khalidi in Antakya, Turkey; Editing by Paul Taylor)